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Review Article

Bone morphogenetic protein signaling in breast cancer progression

ORCID Icon, ORCID Icon & ORCID Icon
Pages 12-28 | Received 29 Nov 2018, Accepted 26 May 2019, Published online: 05 Jul 2019

References

  • Afrakhte, M., A. Morén, S. Jossan, S. Itoh, K. Sampath, B. Westermark, C. H. Heldin, et al. 1998. “Induction of Inhibitory Smad6 and Smad7 mRNA by TGF-β Family Members.” Biochemical and Biophysical Research Communications 249 (2): 505–511.
  • Ai, H., W. Zhou, Z. Wang, G. Qiong, Z. Chen, and S. Deng. 2018. “microRNAs-107 Inhibited Autophagy, Proliferation, and Migration of Breast Cancer Cells by Targeting HMGB1.” Journal of Cellular Biochemistry 120:8696–8705.
  • Alarmo, E. L., and A. Kallioniemi. 2010. “Bone Morphogenetic Proteins in Breast Cancer: Dual Role in Tumourigenesis.” Endocrine-Related Cancer 17 (2): R123–139.
  • Alarmo, E. L., H. Huhtala, T. Korhonen, L. Pylkkänen, K. Holli, T. Kuukasjärvi, S. Parkkila, et al. 2013. “Bone Morphogenetic Protein 4 Expression in Multiple Normal and Tumor Tissues Reveals Its Importance beyond Development.” Modern Pathology 26 (1): 10.
  • Alarmo, E. L., T. Korhonen, T. Kuukasjärvi, H. Huhtala, K. Holli, and A. Kallioniemi. 2008. “Bone Morphogenetic Protein 7 Expression Associates with Bone Metastasis in Breast Carcinomas.” Annals of Oncology 19 (2): 308–314.
  • Alarmo, E. L., T. Kuukasjärvi, R. Karhu, and A. Kallioniemi. 2007. “A Comprehensive Expression Survey of Bone Morphogenetic Proteins in Breast Cancer Highlights the Importance of BMP4 and BMP7.” Breast Cancer Research and Treatment 103 (2): 239–246.
  • Ampuja, M., R. Jokimäki, K. Juuti-Uusitalo, A. Rodriguez-Martinez, E. L. Alarmo, and A. Kallioniemi. 2013. “BMP4 Inhibits the Proliferation of Breast Cancer Cells and Induces an MMP-Dependent Migratory Phenotype in MDA-MB-231 Cells in 3D Environment.” BMC Cancer 13 (1): 429.
  • Bach, D. H., H. Park, and S. Lee. 2018. “The Dual Role of Bone Morphogenetic Proteins in Cancer.” Molecular Therapy – Oncolytics 8: 1–13.
  • Balboni, A. L., P. Cherukuri, M. Ung, A. J. DeCastro, C. Cheng, and J. DiRenzo. 2015. “p53 and ΔNp63α Coregulate the Transcriptional and Cellular Response to TGFβ and BMP Signals.” Molecular Cancer Research 13 (4): 732–742.
  • Balboni, A. L., J. A. Hutchinson, A. J. DeCastro, P. Cherukuri, K. Liby, M. B. Sporn, G. N. Schwartzet al., 2013. “ΔNp63α-Mediated Activation of Bone Morphogenetic Protein Signaling Governs Stem Cell Activity and Plasticity in Normal and Malignant Mammary Epithelial Cells.” Cancer Research 73 (2): 1020–1030.
  • Batlle, E., and H. Clevers. 2017. “Cancer Stem Cells Revisited.” Nature Medicine 23 (10): 1124–1134.
  • Bier, E., and E. M. De Robertis. 2015. “Embryo Development. BMP Gradients: A Paradigm for Morphogen-Mediated Developmental Patterning.” Science 348 (6242): aaa5838.
  • Bokobza, S. M., L. Ye, H. E. Kynaston, R. E. Mansel, and W. G. Jiang. 2009. “Reduced Expression of BMPR-IB Correlates with Poor Prognosis and Increased Proliferation of Breast Cancer Cells.” Cancer Genomics and Proteomics 6 (2): 101–108.
  • Bond, A. M., O. G. Bhalala, and J. A. Kessler. 2012. “The Dynamic Role of Bone Morphogenetic Proteins in Neural Stem Cell Fate and Maturation.” Developmental Neurobiology 72 (7): 1068–1084.
  • Bragdon, B., O. Moseychuk, S. Saldanha, D. King, J. Julian, and A. Nohe. 2011. “Bone Morphogenetic Proteins: A Critical Review.” Cellular Signalling 23 (4): 609–620.
  • Buijs, J. T., G. van der Horst, C. van den Hoogen, H. Cheung, B. de Rooij, J. Kroon, M. Petersenet al., 2012. “The BMP2/7 Heterodimer Inhibits the Human Breast Cancer Stem Cell Subpopulation and Bone Metastases Formation.” Oncogene 31 (17): 2164–2174.
  • Buijs, J. T., N. V. Henriquez, P. G. M. van Overveld, G. van der Horst, I. Que, R. Schwaninger, C. Rentschet al., 2007. “Bone Morphogenetic Protein 7 in the Development and Treatment of Bone Metastases from Breast Cancer.” Cancer Research 67 (18): 8742–8751.
  • Cao, Y., C. Y. Slaney, B. N. Bidwell, B. S. Parker, C. N. Johnstone, J. Rautela, B. L. Eckhardtet al., 2014. “BMP4 Inhibits Breast Cancer Metastasis by Blocking Myeloid-Derived Suppressor Cell Activity.” Cancer Research 74 (18): 5091–5102.
  • Cassar, L., C. Nicholls, A. R. Pinto, R. Chen, L. Wang, H. Li., and J. Liu. 2017. “TGF-Beta Receptor Mediated Telomerase Inhibition, Telomere Shortening and Breast Cancer Cell Senescence.” Protein and Cell 8 (1): 39–54.
  • Chapellier, M., E. Bachelard-Cascales, X. Schmidt, F. Clément, I. Treilleux, E. Delay, A. Jammotet al., 2015. “Disequilibrium of BMP2 Levels in the Breast Stem Cell Niche Launches Epithelial Transformation by Overamplifying BMPR1B Cell Response.” Stem Cell Reports 4 (2): 239–254.
  • Chen, L., Y. Li, Y. Fu, J. Peng, M. H. Mo, M. Stamatakos., C. B. Tealet al., 2013. “Role of Deregulated microRNAs in Breast Cancer Progression Using FFPE Tissue.” PLoS ONE 8 (1): e54213.
  • Clément, F., X. Xu, C. F. Donini, A. Clément, S. Omarjee, E. Delay, I. Treilleux, et al. 2016. “Long-Term Exposure to Bisphenol a or Benzo(a)Pyrene Alters the Fate of Human Mammary Epithelial Stem Cells in Response to BMP2 and BMP4, by Pre-Activating BMP Signaling.” Cell Death and Differentiation 24 (1): 155–166.
  • Clement, J. H., N. Marr, A. Meissner, M. Schwalbe, W. Sebald, K. O. Kliche, K. Höffken, and S. Wölfl. 2000. “Bone Morphogenetic Protein 2 (BMP-2) Induces Sequential Changes of Id Gene Expression in the Breast Cancer Cell Line MCF-7.” Journal of Cancer Research and Clinical Oncology 126 (5): 271–279.
  • Cyr-Depauw, C., J. J. Northey, S. Tabariès, M. G. Annis, Z. Dong, S. Cory, M. Hallett, et al. 2016. “Chordin-Like 1 Suppresses Bone Morphogenetic Protein 4-Induced Breast Cancer Cell Migration and Invasion.” Molecular and Cellular Biology 36 (10): 1509–1525.
  • Dai, K., F. Qin, H. Zhang, X. Liu, C. Guo, M. Zhang, F. Gu, et al. 2015. “Low Expression of BMPRIB Indicates Poor Prognosis of Breast Cancer and Is Insensitive to Taxane-Anthracycline Chemotherapy.” Oncotarget 7 (4): 4770–4784.
  • Daly, A. C., R. A. Randall, and C. S. Hill. 2008. “Transforming Growth Factor β-Induced Smad1/5 Phosphorylation in Epithelial Cells is Mediated by Novel Receptor Complexes and Is Essential for Anchorage-Independent Growth.” Molecular and Cellular Biology 28 (22): 6889–6902.
  • Davis, B. N., A. C. Hilyard, G. Lagna, and A. Hata. 2008. “SMAD Proteins Control DROSHA-Mediated microRNA Maturation.” Nature 454 (7200): 56–61.
  • Davis, B. N., A. C. Hilyard, P. H. Nguyen, G. Lagna, and A. Hata. 2010. “Smad Proteins Bind a Conserved RNA Sequence to Promote MicroRNA Maturation by Drosha.” Molecular Cell 39 (3): 373–384.
  • de Boeck, M., C. Cui, A. A. Mulder, C. R. Jost, S. Ikeno, and P. ten Dijke. 2016. “Smad6 Determines BMP-Regulated Invasive Behaviour of Breast Cancer Cells in a Zebrafish Xenograft Model.” Scientific Reports 6 (1): 24968.
  • Dinami, R., V. Buemi, R. Sestito, A. Zappone, Y. Ciani, M. Mano, E. Pettiet al., 2017. “Epigenetic Silencing of miR-296 and miR-512 Ensures hTERT Dependent Apoptosis Protection and Telomere Maintenance in Basal-Type Breast Cancer Cells.” Oncotarget 8 (56): 95674–95691.
  • Du, J., S. Yang, D. An, F. Hu, W. Yuan, C. Zhai, and T. Zhu. 2009. “BMP-6 Inhibits MicroRNA-21 Expression in Breast Cancer through Repressing δEF1 and AP-1.” Cell Research 19 (4): 487–496.
  • Du, J., S. Yang, Z. Wang, C. Zhai, W. Yuan, R. Lei, J. Zhang, et al. 2008. “Bone Morphogenetic Protein 6 Inhibit Stress‐Induced Breast Cancer Cells Apoptosis via Both Smad and P38 Pathways.” Journal of Cellular Biochemistry 103 (5): 1584–1597.
  • Farnsworth, R. H., T. Karnezis, R. Shayan, M. Matsumoto, C. J. Nowell, M. G. Achen, S. A. Stacker, et al. 2011. “A Role for Bone Morphogenetic Protein-4 in Lymph Node Vascular Remodeling and Primary Tumor Growth.” Cancer Research 71 (20): 6547–6557.
  • Fidler, I. J. 2003. “The Pathogenesis of Cancer Metastasis: The ‘Seed and Soil’ Hypothesis Revisited.” Nature Reviews Cancer 3 (6): 453–458.
  • Flanders, K. C., C. D. Heger, C. Conway, B. Tang, M. Sato, S. L. Dengler, P. K. Goldsmith, S. M. Hewitt, and L. M. Wakefield. 2014. “Brightfield Proximity Ligation Assay Reveals Both Canonical and Mixed Transforming Growth Factor-β/Bone Morphogenetic Protein Smad Signaling Complexes in Tissue Sections.” Journal of Histochemistry and Cytochemistry 62 (12): 846–863.
  • Fong, Y. C., T. M. Li, C. M. Wu, S. F. Hsu, S. T. Kao, R. J. Chen, C. C. Linet al., 2008. “BMP‐2 Increases Migration of Human Chondrosarcoma Cells via PI3K/Akt Pathway.” Journal of Cellular Physiology 217 (3): 846–855.
  • Gao, B., S. Hao, W. Tian, Y. Jiang, S. Zhang, L. Guo, J. Zhao , G. Zhang , J. Yan , and D. Luo. 2017. “MicroRNA-107 is Downregulated and Having Tumor Suppressive Effect in Breast Cancer by Negatively Regulating Brain-Derived Neurotrophic Factor.” The Journal of Gene Medicine 19 (12): e2932.
  • Gao, H., G. Chakraborty, A. P. Lee-Lim, Q. Mo, M. Decker, A. Vonica, R. Shenet al., 2012. “The BMP Inhibitor Coco Reactivates Breast Cancer Cells at Lung Metastatic Sites.” Cell 150 (4): 764–779.
  • Gautschi, O., C. G. Tepper, P. R. Purnell, Y. Izumiya, C. P. Evans, T. P. Green, P. Y. Desprez, et al. 2008. “Regulation of Id1 Expression by Src: Implications for Targeting of the Bone Morphogenetic Protein Pathway in Cancer.” Cancer Research 68 (7): 2250–2258.
  • Ghosh-Choudhury, N., G. Ghosh-Choudhury, A. Celeste, P. M. Ghosh, M. Moyer, S. L. Abboud, J. Kreisberg, et al. 2000. “Bone Morphogenetic Protein-2 Induces Cyclin Kinase Inhibitor p21 and Hypophosphorylation of Retinoblastoma Protein in Estradiol-Treated MCF-7 Human Breast Cancer Cells.” Biochimica et Biophysica Acta 1497 (2): 186–196.
  • Ghosh-Choudhury, N., K. Woodruff, W. Qi, A. Celeste, S. L. Abboud, and G. Choudhury. 2000. “Bone Morphogenetic Protein-2 Blocks MDA MB 231 Human Breast Cancer Cell Proliferation by Inhibiting Cyclin-Dependent Kinase-Mediated Retinoblastoma Protein Phosphorylation.” Biochemical and Biophysical Research Communications 272 (3): 705–711.
  • Goto, K., Y. Kamiya, T. Imamura, K. Miyazono, and K. Miyazawa. 2007. “Selective Inhibitory Effects of Smad6 on Bone Morphogenetic Protein Type I Receptors.” Journal of Biological Chemistry 282 (28): 20603–20611.
  • Gumireddy, K., A. Li, A. V. Kossenkov, K. Q. Cai, Q. Liu, J. Yan, H. Xuet al., 2014. “ID1 Promotes Breast Cancer Metastasis by S100A9 Regulation.” Molecular Cancer Research: MCR 12 (9): 1334–1343.
  • Guo, D., J. Huang, and J. Gong. 2012. “Bone Morphogenetic Protein 4 (BMP4) is Required for Migration and Invasion of Breast Cancer.” Molecular and Cellular Biochemistry 363 (1–2): 179–190.
  • Guo, S. J., H. X. Zeng, P. Huang, S. Wang, C. H. Xie, and S. J. Li. 2018. “MiR-508-3p Inhibits Cell Invasion and Epithelial-Mesenchymal Transition by Targeting ZEB1 in Triple-Negative Breast Cancer.” European Review for Medical and Pharmacological Sciences 22 (19): 6379–6385.
  • Guo, X., and X. F. Wang. 2009. “Signaling Cross-Talk between TGF-β/BMP and Other Pathways.” Cell Research 19 (1): 71–88.
  • Gupta, G. P., J. Perk, S. Acharyya, P. de Candia, V. Mittal, K. Todorova-Manova, W. L. Gerald, et al. 2007. “ID Genes Mediate Tumor Reinitiation during Breast Cancer Lung Metastasis.” Proceedings of the National Academy of Sciences of the United States of America 104 (49): 19506–19511.
  • Han, M., F. Wang, Y. Gu, X. Pei, G. Guo, C. Yu, L. I. N. Li, et al. 2016. “MicroRNA-21 Induces Breast Cancer Cell Invasion and Migration by Suppressing Smad7 via EGF and TGF-β Pathways.” Oncology Reports 35 (1): 73–80.
  • Hawinkels, L. J. A. C., A. G. de Vinuesa, M. Paauwe, M. Kruithof-de Julio, E. Wiercinska, E. Pardali, L. Mezzanotte, et al. 2016. “Activin Receptor-like Kinase 1 Ligand Trap Reduces Microvascular Density and Improves Chemotherapy Efficiency to Various Solid Tumors.” Clinical Cancer Research 22 (1): 96–106.
  • He, T., F. Qi, L. Jia, S. Wang, N. Song, L. Guo, Y. Fu, et al. 2014. “MicroRNA-542-3p Inhibits Tumour Angiogenesis by Targeting Angiopoietin-2.” The Journal of Pathology 232 (5): 499–508.
  • Helms, M. W., J. Packeisen, C. August, B. Schittek, W. Boecker, B. H. Brandt, H. Buergeret al., 2005. “First Evidence Supporting a Potential Role for the BMP/SMAD Pathway in the Progression of Oestrogen Receptor‐Positive Breast Cancer.” The Journal of Pathology 206 (3): 366–376.
  • Hoesel, B., and J. A. Schmid. 2013. “The Complexity of NF-κB Signaling in Inflammation and Cancer.” Molecular Cancer 12 (1): 86.
  • Holtzhausen, A., C. Golzio, T. How, Y. H. Lee, W. P. Schiemann, N. Katsanis, G. C. Blobe, et al. 2014. “Novel Bone Morphogenetic Protein Signaling through Smad2 and Smad3 to Regulate Cancer Progression and Development.” The FASEB Journal 28 (3): 1248–1267.
  • Hong, S., S. Lim, A. G. Li, C. Lee, Y. S. Lee, E. K. Lee, S. H. Park, et al. 2007. “Smad7 Binds to the Adaptors TAB2 and TAB3 to Block Recruitment of the Kinase TAK1 to the Adaptor TRAF2.” Nature Immunology 8 (5): 504–513.
  • Hu, F. E. N., Y. Zhang, M. I. Li, L. Zhao, J. Chen, S. Yang, X. Zhanget al., 2016. “BMP-6 Inhibits the Metastasis of MDA-MB-231 Breast Cancer Cells by Regulating MMP-1 Expression.” Oncology Reports 35 (3): 1823–1830.
  • Hu, F., X. Meng, Q. Tong, L. Liang, R. Xiang, T. Zhu, S. Yanget al., 2013. “BMP-6 Inhibits Cell Proliferation by Targeting microRNA-192 in Breast Cancer.” Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1832 (12): 2379–2390.
  • Huang, P., A. Chen, W. He, Z. Li, G. Zhang, Z. Liu, G. Liuet al., 2017. “BMP-2 Induces EMT and Breast Cancer Stemness through Rb and CD44.” Cell Death Discovery 3: 17039.
  • Jin, H., J. Pi, X. Huang, F. Huang, W. Shao, S. Li, Y. Chenet al., 2012. “BMP2 Promotes Migration and Invasion of Breast Cancer Cells via Cytoskeletal Reorganization and Adhesion Decrease: An AFM Investigation.” Applied Microbiology and Biotechnology 93 (4): 1715–1723.
  • Jiramongkolchai, P., P. Owens, and C. C. Hong. 2016. “Emerging Roles of the Bone Morphogenetic Protein Pathway in Cancer: Potential Therapeutic Target for Kinase Inhibition.” Biochemical Society Transactions 44 (4): 1117–1134.
  • Kang, M., J. Kim, J. Seo, S. Oh, and Y. A. Yoo. 2010. “BMP2 Accelerates the Motility and Invasiveness of Gastric Cancer Cells via Activation of the Phosphatidylinositol 3-Kinase (PI3K)/Akt Pathway.” Experimental Cell Research 316 (1): 24–37.
  • Katsuno, Y., A. Hanyu, H. Kanda, Y. Ishikawa, F. Akiyama, T. Iwase, E. Ogata, S. Ehata, K. Miyazono, and T. Imamura. 2008. “Bone Morphogenetic Protein Signaling Enhances Invasion and Bone Metastasis of Breast Cancer Cells through Smad Pathway.” Oncogene 27 (49): 6322–6333.
  • Kim, E. K., and E. J. J. Choi. 2015. “Compromised MAPK Signaling in Human Diseases: An Update.” Archives of Toxicology 89 (6): 867–882.
  • Kowanetz, M., U. Valcourt, R. Bergström, C. H. Heldin, and A. Moustakas. 2004. “Id2 and Id3 Define the Potency of Cell Proliferation and Differentiation Responses to Transforming Growth Factor Beta and Bone Morphogenetic Protein.” Molecular and Cellular Biology 24 (10): 4241–4254.
  • Kurozumi, K., M. Nishita, K. Yamaguchi, T. Fujita, N. Ueno, and H. Shibuya. 1998. “BRAM1, a BMP Receptor‐Associated Molecule Involved in BMP Signalling.” Genes to Cells 3 (4): 257–264.
  • Lagna, G., A. Hata, A. Hemmati-Brivanlou, and J. Massagué. 1996. “Partnership between DPC4 and SMAD Proteins in TGF-Beta Signalling Pathways.” Nature 383 (6603): 832–836.
  • Lasorella, A., R. Benezra, and A. Iavarone. 2014. “The ID Proteins: Master Regulators of Cancer Stem Cells and Tumour Aggressiveness.” Nature Reviews Cancer 14 (2): 77–91.
  • Laulan, N., and Y. St-Pierre. 2015. “Bone Morphogenetic Protein 4 (BMP-4) and Epidermal Growth Factor (EGF) Inhibit Metalloproteinase-9 (MMP-9) Expression in Cancer Cells.” Oncoscience 2 (3): 309.
  • Lebrun, J. J. 2012. “The Dual Role of TGFβ in Human Cancer: From Tumor Suppression to Cancer Metastasis.” ISRN Molecular Biology 2012: 1–28.
  • Li, Q., L. Wu, D. K. Oelschlager, M. Wan, C. R. Stockard, W. E. Grizzle, N. Wanget al., 2005. “Smad4 Inhibits Tumor Growth by Inducing Apoptosis in Estrogen Receptor-α-Positive Breast Cancer Cells.” Journal of Biological Chemistry 280 (29): 27022–27028.
  • Li, S., H. Dai, Y. He, S. Peng, T. Zhu, Y. Wu, C. Li, and K. Wang. 2018. “BMP9 Inhibits the Growth of Breast Cancer Cells by Downregulation of the PI3K/Akt Signaling Pathway.” Oncology Reports 40 (3): 1743–1751.
  • Lian, W. J., G. Liu, Y. J. Liu, Z. W. Zhao, T. Yi, and H. Y. Zhou. 2013. “Downregulation of BMP6 Enhances Cell Proliferation and Chemoresistance via Activation of the ERK Signaling Pathway in Breast Cancer.” Oncology Reports 30 (1): 193–200.
  • Liu, F., N. Bloch, K. R. Bhushan, A. M. Grand, E. Tanaka, S. Solazzo, P. M. Mertynaet al., 2008. “Humoral Bone Morphogenetic Protein 2 is Sufficient for Inducing Breast Cancer Microcalcification.” Molecular Imaging 7 (4): 175–186.
  • Liu, F., P. Misra, E. P. Lunsford, J. T. Vannah, Y. Liu, R. E. Lenkinski, J. V. Frangioni, et al. 2010. “A Dose- and Time-Controllable Syngeneic Animal Model of Breast Cancer Microcalcification.” Breast Cancer Research and Treatment 122 (1): 87–94.
  • Liu, G., Y. J. Liu, W. J. Lian, Z. W. Zhao, T. Yi, and H. Y. Zhou. 2014. “Reduced BMP6 Expression by DNA Methylation Contributes to EMT and Drug Resistance in Breast Cancer Cells.” Oncology Reports 32 (2): 581–588.
  • Liu, I. M., S. H. Schilling, K. A. Knouse, L. Choy, R. Derynck, and X. F. Wang. 2009. “TGFβ‐Stimulated Smad1/5 Phosphorylation Requires the ALK5 L45 Loop and Mediates the Pro‐Migratory TGFβ Switch.” The EMBO Journal 28 (2): 88–98.
  • Liu, X., J. Yue, R. S. Frey, Q. Zhu, and K. M. Mulder. 1998. “Transforming Growth Factor Beta Signaling through Smad1 in Human Breast Cancer Cells.” Cancer Research 58 (20): 4752–4757.
  • Liu, Y., R. X. Zhang, W. Yuan, H. Q. Chen, D. D. Tian, H. Li, X. Jianget al., 2018. “Knockdown of Bone Morphogenetic Proteins Type 1a Receptor (BMPR1a) in Breast Cancer Cells Protects Bone from Breast Cancer-Induced Osteolysis by Suppressing RANKL Expression.” Cellular Physiology and Biochemistry 45 (5): 1759–1771.
  • Lu, M., S. C. Lin, Y. Huang, Y. J. Kang, R. Rich, Y. C. Lo, D. Myszkaet al., 2007. “XIAP Induces NF-κB Activation via the BIR1/TAB1 Interaction and BIR1 Dimerization.” Molecular Cell 26 (5): 689–702.
  • Martin, Y., D. Park, A. Ramachandran, L. Ombrato, F. Calvo, P. Chakravarty, B. Spencer-Dene.et al., 2015. “Mesenchymal Cancer Cell-Stroma Crosstalk Promotes Niche Activation, Epithelial Reversion, and Metastatic Colonization.” Cell Reports 13 (11): 2456–2469.
  • Martínez, V. G., C. Rubio, M. Martínez-Fernández, C. Segovia, F. López-Calderón, M. Garín, A. Teijeira et al.., 2017. “BMP4 Induces M2 Macrophage Polarization and Favors Tumor Progression in Bladder Cancer.” Clinical Cancer Research 23 (23): 7388–7399.
  • Masuda, H., F. Otsuka, Y. Matsumoto, M. Takano, T. Miyoshi, K. Inagaki, T. Shien, et al. 2011. “Functional Interaction of Fibroblast Growth Factor-8, Bone Morphogenetic Protein and Estrogen Receptor in Breast Cancer Cell Proliferation.” Molecular and Cellular Endocrinology 343 (1–2): 7–17.
  • Matsumoto, Y., F. Otsuka, J. Hino, T. Miyoshi, M. Takano, M. Miyazato, H. Makino, et al. 2012. “Bone Morphogenetic Protein-3b (BMP-3b) Inhibits Osteoblast Differentiation via Smad2/3 Pathway by Counteracting Smad1/5/8 Signaling.” Molecular and Cellular Endocrinology 350 (1): 78–86.
  • Mitchell, D., E. G. Pobre, A. W. Mulivor, A. V. Grinberg, R. Castonguay, T. E. Monnell, N. Solbanet al., 2010. “ALK1-Fc Inhibits Multiple Mediators of Angiogenesis and Suppresses Tumor Growth.” Molecular Cancer Therapeutics 9 (2): 379–388.
  • Miyazawa, K., and K. Miyazono. 2016. “Regulation of TGF-β Family Signaling by Inhibitory Smads.” Cold Spring Harbor Perspectives in Biology 9 (3): a022095.
  • Molina, C. A., R. Sarabia-Estrada, Z. L. Gokaslan, T. F. Witham, A. Bydon, J. P. Wolinsky, D. M. Sciubba, et al. 2012. “Delayed Onset of Paralysis and Slowed Tumor Growth Following in Situ Placement of Recombinant Human Bone Morphogenetic Protein 2 within Spine Tumors in a Rat Model of Metastatic Breast Cancer.” Journal of Neurosurgery: Spine 16 (4): 365–372.
  • Montesano, R., R. Sarközi, and H. Schramek. 2008. “Bone Morphogenetic Protein-4 Strongly Potentiates Growth Factor-Induced Proliferation of Mammary Epithelial Cells.” Biochemical and Biophysical Research Communications 374 (1): 164–168.
  • Naber, H. P. H., E. Wiercinska, E. Pardali, T. van Laar, E. Nirmala, A. Sundqvist, H. van Dam, et al. 2012. “BMP-7 Inhibits TGF-β-Induced Invasion of Breast Cancer Cells through Inhibition of Integrin β3 Expression.” Cellular Oncology 35 (1): 19–28.
  • Nakao, A., M. Afrakhte, A. Morn, T. Nakayama, J. L. Christian, R. Heuchel, S. Itoh, et al. 1997. “Identification of Smad7, a TGFβ-Inducible Antagonist of TGF-β Signalling.” Nature 389 (6651): 39369.
  • National Cancer Institute. 2018. “Table 4.13: 5-Year Relative and Period Survival.” In SEER Cancer Statistics Review, 1975–2015, edited by A. M. Noone, N. Howlader, M. Krapcho, D. Miller, A. Brest, M. Yu, J. Ruhl, Z. Tatalovich, A. Mariotto, D. R. Lewis, H. S. Chen, E. J. Feuer, and K. A. Cronin, Bethesda, MD: National Cancer Institute. https://seer.cancer.gov/csr/1975_2015/, based on November 2017 SEER data submission, posted to the SEER web site.
  • Neman, J., C. Choy, C. M. Kowolik, A. Anderson, V. J. Duenas, S. Waliany, B. T. Chen, M. Y. Chen, and R. Jandial. 2013. “Co-Evolution of Breast-to-Brain Metastasis and Neural Progenitor Cells.” Clinical and Experimental Metastasis 30 (6): 753–768.
  • Ong, D. B., S. M. Colley, M. R. Norman, S. Kitazawa, and J. H. Tobias. 2004. “Transcriptional Regulation of a BMP‐6 Promoter by Estrogen Receptor α.” Journal of Bone and Mineral Research 19 (3): 447–454.
  • Ouarné, M., C. Bouvard, G. Boneva, C. Mallet, J. Ribeiro, A. Desroches-Castan, E. Soleilhac, E. Tillet, O. Peyruchaud, and S. Bailly. 2018. “BMP9, but Not BMP10, Acts as a Quiescence Factor on Tumor Growth, Vessel Normalization and Metastasis in a Mouse Model of Breast Cancer.” Journal of Experimental and Clinical Cancer Research: CR 37 (1): 209.
  • Owens, P., H. Polikowsky, M. W. Pickup, A. E. Gorska, B. Jovanovic, A. K. Shaw, S. V. Novitskiy, C. C. Hong, and H. L. Moses. 2013. “Bone Morphogenetic Proteins Stimulate Mammary Fibroblasts to Promote Mammary Carcinoma Cell Invasion.” PLoS One 8 (6): e67533.
  • Owens, P., M. W. Pickup, S. V. Novitskiy, A. Chytil, A. E. Gorska, M. E. Aakre, J. West, et al. 2012. “Disruption of Bone Morphogenetic Protein Receptor 2 (BMPR2) in Mammary Tumors Promotes Metastases through Cell Autonomous and Paracrine Mediators.” Proceedings of the National Academy of Sciences 109 (8): 2814–2819.
  • Owens, P., M. W. Pickup, S. V. Novitskiy, J. M. Giltnane, A. E. Gorska, C. R. Hopkins, C. C. Honget al., 2015. “Inhibition of BMP Signaling Suppresses Metastasis in Mammary Cancer.” Oncogene 34 (19): 2437–2449.
  • Pal, A., W. Huang, X. Li, K. A. Toy, Z. Nikolovska-Coleska, and C. G. Kleer. 2012. “CCN6 Modulates BMP Signaling via the Smad-Independent TAK1/p38 Pathway, Acting to Suppress Metastasis of Breast Cancer.” Cancer Research 72 (18): 4818–4828.
  • Park, K. S., M. Dubon, and B. M. Gumbiner. 2015. “N-Cadherin Mediates the Migration of MCF-10A Cells Undergoing Bone Morphogenetic Protein 4-Mediated Epithelial Mesenchymal Transition.” Tumor Biology 36 (5): 3549–3556.
  • Pickup, M. W., L. D. Hover, E. R. Polikowsky, A. Chytil, A. E. Gorska, S. V. Novitskiy, H. L. Moseset al., 2015. “BMPR2 Loss in Fibroblasts Promotes Mammary Carcinoma Metastasis via Increased Inflammation.” Molecular Oncology 9 (1): 179–191.
  • Pickup, M. W., L. D. Hover, Y. Guo, A. E. Gorska, A. Chytil, S. V. Novitskiy, H. L. Moses, and P. Owens. 2015. “Deletion of the BMP Receptor BMPR1a Impairs Mammary Tumor Formation and Metastasis.” Oncotarget 6 (26): 22890–22904.
  • Pouliot, F., and C. Labrie. 2002. “Role of Smad1 and Smad4 Proteins in the Induction of p21WAF1, Cip1 during Bone Morphogenetic Protein-Induced Growth Arrest in Human Breast Cancer Cells.” Journal of Endocrinology 172 (1): 187–198.
  • Qin, W., B. Zhao, Y. Shi, C. Yao, L. Jin, and Y. Jin. 2009. “BMPRII Is a Direct Target of miR-21.” Acta Biochimica et Biophysica Sinica 41 (7): 618–623.
  • Raida, M., J. H. Clement, K. Ameri, C. Han, R. D. Leek, and A. L. Harris. 2005. “Expression of Bone Morphogenetic Protein 2 in Breast Cancer Cells Inhibits Hypoxic Cell Death.” International Journal of Oncology 26 (6): 1465–1470.
  • Raida, M., J. H. Clement, R. D. Leek, K. Ameri, R. Bicknell, D. Niederwieser, A. L. Harriset al., 2005. “Bone Morphogenetic Protein 2 (BMP-2) and Induction of Tumor Angiogenesis.” Journal of Cancer Research and Clinical Oncology 131 (11): 741–750.
  • Ren, W., Y. Liu, S. Wan, C. Fei, W. Wang, Y. Chen, Z. Zhanget al., 2014. “BMP9 Inhibits Proliferation and Metastasis of HER2-Positive SK-BR-3 Breast Cancer Cells through ERK1/2 and PI3K/AKT Pathways.” PLoS ONE 9 (5): e96816.
  • Richter, J., M. Schlesner, S. Hoffmann, M. Kreuz, E. Leich, B. Burkhardt, M. Rosolowski, et al. 2012. “Recurrent Mutation of the ID3 Gene in Burkitt Lymphoma Identified by Integrated Genome, Exome and Transcriptome Sequencing.” Nature Genetics 44 (12): 1316–1320.
  • Rodriguez-Martinez, A., E. L. Alarmo, L. Saarinen, J. Ketolainen, K. Nousiainen, S. Hautaniemi, and A. Kallioniemi. 2011. “Analysis of BMP4 and BMP7 Signaling in Breast Cancer Cells Unveils Time-Dependent Transcription Patterns and Highlights a Common Synexpression Group of Genes.” BMC Medical Genomics 4 (1): 1–16.
  • Romagnoli, M., K. Belguise, Z. Yu, X. Wang, E. Landesman-Bollag, D. C. Seldin, D. Chalbos, et al. 2012. “Epithelial-to-Mesenchymal Transition Induced by TGF-β1 Is Mediated by Blimp-1–Dependent Repression of BMP-5.” Cancer Research 72 (23): 6268–6278.
  • Rose, M., S. K. Meurer, V. Kloten, R. Weiskirchen, B. Denecke, W. Antonopoulos, M. Deckert, et al. 2018. “ITIH5 Induces a Shift in TGF‐β Superfamily Signaling Involving Endoglin and Reduces Risk for Breast Cancer Metastasis and Tumor Death.” Molecular Carcinogenesis 57 (2): 167–181.
  • Sakai, H., M. Furihata, C. Matsuda, M. Takahashi, H. Miyazaki, T. Konakahara, T. Imamura, and T. Okada. 2012. “Augmented Autocrine Bone Morphogenic Protein (BMP) 7 Signaling Increases the Metastatic Potential of Mouse Breast Cancer Cells.” Clinical and Experimental Metastasis 29 (4): 327–338.
  • Salazar, V. S., L. W. Gamer, and V. Rosen. 2016. “BMP Signalling in Skeletal Development, Disease and Repair.” Nature Reviews Endocrinology 12 (4): 203–221.
  • Sanchez-Vega, F., M. Mina, J. Armenia, W. K. Chatila, A. Luna, K. C. La, S. Dimitriadoy, et al. 2018. “Oncogenic Signaling Pathways in the Cancer Genome Atlas.” Cell 173 (2): 321.
  • Sapkota, G., C. Alarcón, F. M. Spagnoli, A. H. Brivanlou, and J. Massagué. 2007. “Balancing BMP Signaling through Integrated Inputs into the Smad1 Linker.” Molecular Cell 25 (3): 441–454.
  • Schwalbe, M., J. Sänger, R. Eggers, A. Naumann, A. Schmidt, K. Höffken, and J. H. Clement. 2003. “Differential Expression and Regulation of Bone Morphogenetic Protein 7 in Breast Cancer.” International Journal of Oncology 23 (1): 89–95.
  • Shee, K., A. Jiang, F. S. Varn, S. Liu, N. A. Traphagen, P. Owens., C. X. Maet al., 2019. “Cytokine Sensitivity Screening Highlights BMP4 Pathway Signaling as a Therapeutic Opportunity in ER + Breast Cancer.” FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology 33 (2): 1644–1657.
  • Shim, J. H., C. Xiao, A. E. Paschal, S. T. Bailey, P. Rao, M. S. Hayden, K. Y. Lee., et al. 2005. “TAK1, but Not TAB1 or TAB2, Plays an Essential Role in Multiple Signaling Pathways in Vivo.” Genes and Development 19 (22): 2668–2681.
  • Shim, J. H., M. B. Greenblatt, M. Xie, M. D. Schneider, W. Zou, B. Zhai, S. Gygiet al., 2009. “TAK1 is an Essential Regulator of BMP Signalling in Cartilage.” The EMBO Journal 28 (14): 2028–2041.
  • Sieber, C., J. Kopf, C. Hiepen, and P. Knaus. 2009. “Recent Advances in BMP Receptor Signaling.” Cytokine and Growth Factor Reviews 20 (5–6): 343–355.
  • Song, K. H., M. Park, T. S. Nandu, S. Gadad, S. C. Kim, and M. Y. Kim. 2016. “GALNT14 Promotes Lung-Specific Breast Cancer Metastasis by Modulating Self-Renewal and Interaction with the Lung Microenvironment.” Nature Communications 7:13796.
  • Stighall, M., C. Manetopoulos, H. Axelson, and G. Landberg. 2005. “High ID2 Protein Expression Correlates with a Favourable Prognosis in Patients with Primary Breast Cancer and Reduces Cellular Invasiveness of Breast Cancer Cells.” International Journal of Cancer 115 (3): 403–411.
  • Stolfi, C., I. Marafini, V. Simone, F. Pallone, and G. Monteleone. 2013. “The Dual Role of Smad7 in the Control of Cancer Growth and Metastasis.” International Journal of Molecular Sciences 14 (12): 23774–23790.
  • Su, J. L., C. Y. Yang, M. Zhao, M. L. Kuo, and M. L. Yen. 2007. “Forkhead Proteins Are Critical for Bone Morphogenetic Protein-2 Regulation and anti-Tumor Activity of Resveratrol.” Journal of Biological Chemistry 282 (27): 19385–19398.
  • Takahashi, M., F. Otsuka, T. Miyoshi, H. Otani, J. Goto, M. Yamashita, T. Ogura, et al. 2008. “Bone Morphogenetic Protein 6 (BMP6) and BMP7 Inhibit Estrogen-Induced Proliferation of Breast Cancer Cells by Suppressing p38 Mitogen-Activated Protein Kinase Activation.” Journal of Endocrinology 199 (3): 445–455.
  • Tan, C. C., G. X. Li, L. D. Tan, X. Du, X. Q. Li, R. He, Q. S. Wang, and Y. M. Feng. 2016. “Breast Cancer Cells Obtain an Osteomimetic Feature via Epithelial-Mesenchymal Transition That Have Undergone BMP2/RUNX2 Signaling Pathway Induction.” Oncotarget 5 (0): 79688–79705.
  • Tarragona, M., M. Pavlovic, A. Arnal-Estapé, J. Urosevic, M. Morales, M. Guiu, E. Planet, et al. 2012. “Identification of NOG as a Specific Breast Cancer Bone Metastasis-Supporting Gene.” Journal of Biological Chemistry 287 (25): 21346–21355.
  • Torre, L. A., F. Bray, R. L. Siegel, J. Ferlay, J. Lortet‐Tieulent, and A. Jemal. 2015. “Global Cancer Statistics, 2012.” CA: A Cancer Journal for Clinicians 65 (2): 87–108.
  • Urist, M. R. 1965. “Bone: Formation by Autoinduction.” Science 150 (3698): 893–899.
  • van den Wijngaard, A., W. R. Mulder, R. Dijkema, C. J. C. Boersma, S. Mosselman, E. J. J. van Zoelen, W. Olijve, et al. 2000. “Antiestrogens Specifically up-Regulate Bone Morphogenetic Protein-4 Promoter Activity in Human Osteoblastic Cells.” Molecular Endocrinology (Baltimore, MD) 14 (5): 623–633.
  • Voorneveld, P. W., L. L. Kodach, R. J. Jacobs, N. Liv, A. C. Zonnevylle, J. P. Hoogenboom, I. Biemond, et al. 2014. “Loss of SMAD4 Alters BMP Signaling to Promote Colorectal Cancer Cell Metastasis via Activation of Rho and ROCK.” Gastroenterology 147 (1): 196.
  • Voorneveld, P. W., V. Stache, R. J. Jacobs, E. Smolders, A. I. Sitters, A. Liesker, K. S. Korkmaz, et al. 2013. “Reduced Expression of Bone Morphogenetic Protein Receptor IA in Pancreatic Cancer Is Associated with a Poor Prognosis.” British Journal of Cancer 109 (7): 1805–1812.
  • Wang, C., F. Hu, S. Guo, D. Mi, W. Shen, J. Zhang, Y. Qiaoet al., 2011. “BMP-6 Inhibits MMP-9 Expression by Regulating Heme Oxygenase-1 in MCF-7 Breast Cancer Cells.” Journal of Cancer Research and Clinical Oncology 137 (6): 985–995.
  • Wang, D., P. Huang, O. Zhu, L. I. Sun, Q. Huang, and J. U. Wang. 2012. “Induction of Estrogen Receptor α-36 Expression by Bone Morphogenetic Protein 2 in Breast Cancer Cell Lines.” Molecular Medicine Reports 6 (3): 591–596.
  • Wang, J., S. Sun, J. Zhang, and G. Wang. 2017. “Prognostic Value of Circulating microRNA-21 for Breast Cancer: A Systematic Review and Meta-Analysis.” Artificial Cells, Nanomedicine, and Biotechnology 45 (6): 1–6.
  • Wang, K., H. Feng, W. Ren, X. Sun, J. Luo, M. Tang, L. Zhouet al., 2011. “BMP9 Inhibits the Proliferation and Invasiveness of Breast Cancer Cells MDA-MB-231.” Journal of Cancer Research and Clinical Oncology 137 (11): 1687.
  • Wang, T., Z. Zhang, K. Wang, J. Wang, Y. Jiang, J. Xia, L. Gou., et al. 2017. “Inhibitory Effects of BMP9 on Breast Cancer Cells by Regulating their Interaction with Pre-Adipocytes/Adipocytes.” Oncotarget 5 (0): 35890–35901.
  • Wang, W., Y. Weng, W. Ren, Z. Zhang, T. Wang, J. Wang, Y. Jianget al., 2015. “Biological Roles of Human Bone Morphogenetic Protein 9 in the Bone Microenvironment of Human Breast Cancer MDA-MB-231 Cells.” American Journal of Translational Research 7 (9): 1660–1674.
  • Wang, Y., C. C. Ho, E. Bang, C. A. Rejon, V. Libasci, P. Pertchenko, T. E. Hébertet al., 2014. “Bone Morphogenetic Protein 2 Stimulates Noncanonical SMAD2/3 Signaling via the BMP Type 1A Receptor in Gonadotrope-Like Cells: Implications for FSH Synthesis.” Endocrinology 155 (5): 1970–1981.
  • Wilson, J. W., R. W. Deed, T. Inoue, M. Balzi, A. Becciolini, P. Faraoni, C. S. Potten, and J. D. Norton. 2001. “Expression of Id Helix-Loop-Helix Proteins in Colorectal Adenocarcinoma Correlates with p53 Expression and Mitotic Index.” Cancer Research 61 (24): 8803–8810.
  • Wu, L., Y. Wu, B. Gathings, M. Wan, X. Li, W. Grizzle, Z. Liuet al., 2003. “Smad4 as a Transcription Corepressor for Estrogen Receptor α.” Journal of Biological Chemistry 278 (17): 15192–15200.
  • Yadin, D., P. Knaus, and T. D. Mueller. 2016. “Structural Insights into BMP Receptors: Specificity, Activation and Inhibition.” Cytokine and Growth Factor Reviews 27: 13–34.
  • Yamaguchi, K., S. I Nagai, J. Ninomiya‐Tsuji, M. Nishita, K. Tamai, K. Irie, N. Ueno, E. Nishida, H. Shibuya, and K. Matsumoto. 1999. “XIAP, a Cellular Member of the Inhibitor of Apoptosis Protein Family, Links the Receptors to TAB1–TAK1 in the BMP Signaling Pathway.” The EMBO Journal 18 (1): 179–187.
  • Yamaguchi, K., K. Shirakabe, H. Shibuya, K. Irie, I. Oishi, N. Ueno, T. Taniguchiet al., 1995. “Identification of a Member of the MAPKKK Family as a Potential Mediator of TGF-β Signal Transduction.” Science 270 (5244): 2008–2011.
  • Yamamoto, T., F. Saatcioglu, and T. Matsuda. 2002. “Cross-Talk between Bone Morphogenic Proteins and Estrogen Receptor Signaling.” Endocrinology 143 (7): 2635–2642.
  • Yamawaki, K., Y. Kondo, T. Okada, T. Oshima, M. Kakitani, and K. Tomizuka. 2016. “The Soluble Form of BMPRIB Is a Novel Therapeutic Candidate for Treating Bone Related Disorders.” Scientific Reports 6 (1): 18849.
  • Ye, L., S. Bokobza, J. Li, M. Moazzam, J. Chen, R. E. Mansel, W. G. Jianget al., 2010. “Bone Morphogenetic Protein-10 (BMP-10) Inhibits Aggressiveness of Breast Cancer Cells and Correlates with Poor Prognosis in Breast Cancer.” Cancer Science 101 (10): 2137–2144.
  • Ye, S., B. H. Park, K. J. Song, J. R. Kim, K. Y. Jang, H. S. Park, J. S. Baeet al., 2013. “In Vivo Inhibition of Bone Morphogenetic Protein-2 on Breast Cancer Cell Growth.” Spine 38 (3): E143–150.
  • Ying, X., Y. Sun, and P. He. 2015. “Bone Morphogenetic Protein-7 Inhibits EMT-Associated Genes in Breast Cancer.” Cellular Physiology and Biochemistry 37 (4): 1271–1278.
  • Yue, J., M. T. Hartsough, R. S. Frey, T. Frielle, and K. M. Mulder. 1999. “Cloning and Expression of a Rat Smad1: Regulation by TGFß and Modulation by the Ras/MEK Pathway.” Journal of Cellular Physiology 178 (3): 387–396.
  • Zabkiewicz, C., J. Resaul, R. Hargest, W. G. Jiang, and L. Ye. 2017. “Bone Morphogenetic Proteins, Breast Cancer, and Bone Metastases: Striking the Right Balance.” Endocrine-Related Cancer 24 (10): R349–R366.
  • Zhang, L., Y. Ye, X. Long, P. Xiao, X. Ren, and J. Yu. 2016. “BMP Signaling and Its Paradoxical Effects in Tumorigenesis and Dissemination.” Oncotarget 7 (47): 78206–78218.
  • Zhang, M., J. D. Yan, L. Zhang, Q. Wang, S. J. Lü, J. Zhang, and T. H. Zhu. 2005. “Activation of Bone Morphogenetic Protein-6 Gene Transcription in MCF-7 Cells by Estrogen.” Chinese Medical Journal 118 (19): 1629–1636.
  • Zhao, H. J., C. Klausen, Y. Li, H. Zhu, Y. L. Wang, and P. C. K. Leung. 2018. “Bone Morphogenetic Protein 2 Promotes Human Trophoblast Cell Invasion by Upregulating N-Cadherin via Non-Canonical SMAD2/3 Signaling.” Cell Death and Disease 9 (2): 174.
  • Zhao, X., Z. Duan, X. Liu, B. Wang, X. Wang, J. He, Z. Yaoet al., 2013. “MicroRNA-127 is Downregulated by Tudor-SN Protein and Contributes to Metastasis and Proliferation in Breast Cancer Cell Line MDA-MB-231.” The Anatomical Record 296 (12): 1842–1849.
  • Zhou, Q., J. Heinke, A. Vargas, S. Winnik, T. Krauss, C. Bode, C. Pattersonet al., 2007. “ERK Signaling is a Central Regulator for BMP-4 Dependent Capillary Sprouting.” Cardiovascular Research 76 (3): 390–399.

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