2,689
Views
0
CrossRef citations to date
0
Altmetric
Research Paper

Mutually exclusive teams-like patterns of gene regulation characterize phenotypic heterogeneity along the noradrenergic-mesenchymal axis in neuroblastoma

, , , & ORCID Icon
Article: 2301802 | Received 08 Sep 2023, Accepted 01 Jan 2024, Published online: 17 Jan 2024

References

  • Brodeur GM. Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer. 2003;3(3):203–12. doi:10.1038/nrc1014.
  • Johnsen JI, Dyberg C, Wickström M. 2019. Neuroblastoma—A neural crest derived embryonal malignancy. Front Mol Neurosci. 12:433925. doi: 10.3389/fnmol.2019.00009.
  • Park JR, Eggert A, Caron H. Neuroblastoma: biology, prognosis, and treatment. Hematol Oncol Clin North Am. 2010;24(1):65–86. doi:10.1016/j.hoc.2009.11.011.
  • Greengard EG. Molecularly targeted therapy for neuroblastoma. Children. 2018;5(10):142. doi:10.3390/CHILDREN5100142.
  • Zage PE. Novel therapies for relapsed and refractory neuroblastoma. Children. 2018;5(11):148. doi:10.3390/CHILDREN5110148.
  • Shendy NAM, Zimmerman MW, Abraham BJ, Durbin AD. Intrinsic transcriptional heterogeneity in neuroblastoma guides mechanistic and therapeutic insights. Cell Rep Med. 2022;3(5):100632. doi:10.1016/J.XCRM.2022.100632.
  • Pillai M, Jolly MK. Systems-level network modeling deciphers the master regulators of phenotypic plasticity and heterogeneity in melanoma. iScience. 2021;24(10):103111. doi:10.1016/j.isci.2021.103111.
  • Sharma A, Merritt E, Hu X, Cruz A, Jiang C, Sarkodie H, Zhou Z, Malhotra J, Riedlinger GM, De S. Non-genetic intra-tumor heterogeneity is a major predictor of phenotypic heterogeneity and ongoing evolutionary dynamics in lung tumors. Cell Rep. 2019;29(8):2164–2174.e5. doi:10.1016/j.celrep.2019.10.045.
  • Su Y, Bintz M, Yang Y, Robert L, Ng AHC, Liud V, Ribas A, Heath JR, Wei W, Tanay A. Phenotypic heterogeneity and evolution of melanoma cells associated with targeted therapy resistance. PLoS Comput Biol. 2019;15(6):e1007034. doi:10.1371/journal.pcbi.1007034.
  • Gautier M, Thirant C, Delattre O, Janoueix-Lerosey I. Plasticity in neuroblastoma cell identity defines a noradrenergic-to-mesenchymal transition (Nmt). Cancers Basel. 2021;13(12):2904. doi:10.3390/cancers13122904.
  • Bhatia S, Monkman J, Blick T, Pinto C, Waltham A, Nagaraj SH, Thompson EW. Interrogation of phenotypic plasticity between epithelial and mesenchymal states in breast cancer. J Clin Med. 2019;8(6):893. doi:10.3390/jcm8060893.
  • Chauhan L, Ram U, Hari K, Jolly MK. Topological signatures in regulatory network enable phenotypic heterogeneity in small cell lung cancer. Elife. 2021;10:e64522. doi:10.7554/eLife.64522.
  • Walton JD, Kattan DR, Thomas SK, Spengler BA, Guo HF, Biedler JL, Cheung NKV, Ross RA. Characteristics of stem cells from human neuroblastoma cell lines and in tumors. Neoplasia. 2004;6(6):838. doi:10.1593/NEO.04310.
  • Zeineldin M, Patel AG, Dyer MA. Neuroblastoma: When differentiation goes awry. Neuron. 2022;110(18):2916–2928. doi:10.1016/j.neuron.2022.07.012.
  • Lecca MC, Jonker MA, Kulsoom AU, Uçuç¨uçükosmanoglu AK¨, Van Wieringen W, Westerman BA. Adrenergic to mesenchymal fate switching of neuroblastoma occurs spontaneously in vivo resulting in differential tumorigenic potential. Eur J Mol Clin Med. 2018;1(4):219–226. doi:10.31083/J.JMCM.2018.04.4221.
  • Thirant C, Peltier A, Durand S, Kramdi A, Louis-Brennetot C, Pierre-Eugène C, Gautier M, Costa A, Grelier A, Zaïdi S, et al. Reversible transitions between noradrenergic and mesenchymal tumor identities define cell plasticity in neuroblastoma. Nat Commun. 2023;14(1):1–18. doi:10.1038/s41467-023-38239-5.
  • Van Groningen T, Koster J, Valentijn LJ, Zwijnenburg DA, Akogul N, Hasselt NE, Broekmans M, Haneveld F, Nowakowska NE, Bras J, et al. Neuroblastoma is composed of two super-enhancer-associated differentiation states. Nat Genet. 2017;49(8):1261–1266. doi:10.1038/ng.3899.
  • Kahlert UD, Joseph JV, Kruyt FAE. EMT- and MET-related processes in nonepithelial tumors: importance for disease progression, prognosis, and therapeutic opportunities. Mol Oncol. 2017;11(7):860–877. doi:10.1002/1878-0261.12085.
  • Lourenco AR, Ban Y, Crowley MJ, Lee SB, Ramchandani D, Du W, Elemento O, George JT, Jolly MK, Levine H, et al. Differential contributions of pre- and post-EMT tumor cells in breast cancer metastasis. Cancer Res. 2020;80(2):163–169. doi:10.1158/0008-5472.CAN-19-1427.
  • Pastushenko I, Blanpain C. EMT transition states during tumor progression and metastasis. Trends Cell Biol. 2019;29(3):212–226. doi:10.1016/j.tcb.2018.12.001.
  • Boeva V, Louis-Brennetot C, Peltier A, Durand S, Pierre-Eugène C, Raynal V, Etchevers HC, Thomas S, Lermine A, Daudigeos-Dubus E, et al. Heterogeneity of neuroblastoma cell identity defined by transcriptional circuitries. Nat Genet. 2017;49(9):1408–1413. doi:10.1038/ng.3921.
  • Sahoo S, Nayak SP, Hari K, Purkait P, Mandal S, Kishore A, Levine H, Jolly MK. 2021. Immunosuppressive traits of the hybrid epithelial/mesenchymal phenotype. Front Immunol. 12:797261. doi: 10.3389/fimmu.2021.797261.
  • Simeonov KP, Byrns CN, Clark ML, Norgard RJ, Martin B, Stanger BZ, Shendure J, McKenna A, Lengner CJ. Single-cell lineage tracing of metastatic cancer reveals selection of hybrid EMT states. Cancer Cell. 2021;39(8):1150–1162.e9. doi:10.1016/j.ccell.2021.05.005.
  • Tripathi S, Levine H, Jolly MK. The physics of cellular decision making during epithelial–mesenchymal transition. Annu Rev Biophys. 2020;49(1):1–18. doi:10.1146/annurev-biophys-121219-081557.
  • van Dijk D, Sharma R, Nainys J, Yim K, Kathail P, Carr AJ, Burdziak C, Moon KR, Chaffer CL, Pattabiraman D, et al. Recovering gene interactions from single-cell data using data diffusion. Cell. 2018;174(3):716–729.e27. doi:10.1016/j.cell.2018.05.061.
  • Eisenberg E, Levanon EY. Human housekeeping genes, revisited. Trends Genet. 2013;29(10):569–574. doi:10.1016/j.tig.2013.05.010.
  • Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102(43):15545–15550. doi:10.1073/pnas.0506580102.
  • Liberzon A, Subramanian A, Pinchback R, Thorvaldsdóttir H, Tamayo P, Mesirov JP. Molecular signatures database (MSigDB) 3.0. Bioinformatics. 2011;27(12):1739–1740. doi:10.1093/bioinformatics/btr260.
  • Aibar S, González-Blas CB, Moerman T, Huynh-Thu VA, Imrichova H, Hulselmans G, Rambow F, Marine J-C, Geurts P, Aerts J, et al. SCENIC: single-cell regulatory network inference and clustering. Nat Methods. 2017;14(11):1083–1086. doi:10.1038/nmeth.4463.
  • Puram SV, Tirosh I, Parikh AS, Patel AP, Yizhak K, Gillespie S, Rodman C, Luo CL, Mroz EA, Emerick KS, et al. Single-cell transcriptomic analysis of primary and metastatic tumor ecosystems in head and neck cancer. Cell. 2017;171(7):1611–1624.e24. doi:10.1016/j.cell.2017.10.044.
  • Hari K, Ullanat V, Balasubramanian A, Gopalan A, Jolly MK. Landscape of epithelial mesenchymal plasticity as an emergent property of coordinated teams in regulatory networks. Elife. 2022;11:e76535. doi:10.7554/elife.76535.
  • Chakraborty P, Chen EL, McMullen I, Armstrong AJ, Jolly MK, Somarelli JA. 2021. Analysis of immune subtypes across the epithelial-mesenchymal plasticity spectrum. Comput Struct Biotechnol J. 19:3842–3851. doi: 10.1016/j.csbj.2021.06.023.
  • Nishida Y, Adati N, Ozawa R, Maeda A, Sakaki Y, Takeda T. Identification and classification of genes regulated by phosphatidylinositol 3-kinase- and TRKB-mediated signalling pathways during neuronal differentiation in two subtypes of the human neuroblastoma cell line SH-SY5Y. BMC Res Notes. 2008;1(1):95. doi:10.1186/1756-0500-1-95.
  • Fardin P, Barla A, Mosci S, Rosasco L, Verri A, Versteeg R, Caron HN, Molenaar JJ, Øra I, Eva A, et al. A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients. Mol Cancer. 2010;9(1):185. doi:10.1186/1476-4598-9-185.
  • Middelbeek J, Visser D, Henneman L, Kamermans A, Kuipers AJ, Hoogerbrugge PM, Jalink K, van Leeuwen FN. TRPM7 maintains progenitor-like features of neuroblastoma cells: implications for metastasis formation. Oncotarget. 2015;6(11):8760–8776. doi:10.18632/ONCOTARGET.3315.
  • Gu L, Chu P, Lingeman R, McDaniel H, Kechichian S, Hickey RJ, Liu Z, Yuan YC, Sandoval JA, Fields GB, et al. The mechanism by which MYCN amplification confers an enhanced sensitivity to a PCNA-Derived cell permeable peptide in neuroblastoma cells. EBioMedicine. 2015;2(12):1923–1931. doi:10.1016/J.EBIOM.2015.11.016.
  • Cole KA, Huggins J, Laquaglia M, Hulderman CE, Russell MR, Bosse K, Diskin SJ, Attiyeh EF, Sennett R, Norris G, et al. RNAi screen of the protein kinome identifies checkpoint kinase 1 (CHK1) as a therapeutic target in neuroblastoma. Proc Natl Acad Sci U S A. 2011;108(8):3336–3341. doi:10.1073/pnas.1012351108.
  • Ikegaki N, Shimada H, Fox AM, Regan PL, Jacobs JR, Hicks SL, Rappaport EF, Tang XX. Transient treatment with epigenetic modifiers yields stable neuroblastoma stem cells resembling aggressive large-cell neuroblastomas. Proc Natl Acad Sci U S A. 2013;110(15):6097–6102. doi:10.1073/pnas.1118262110.
  • Debruyne DN, Bhatnagar N, Sharma B, Luther W, Moore NF, Cheung NK, Gray NS, George RE. ALK inhibitor resistance in ALK(F1174L)-driven neuroblastoma is associated with AXL activation and induction of EMT. Oncogene. 2016;35(28):3681–3691. doi:10.1038/ONC.2015.434.
  • Hari K, Harlapur P, Saxena A, Girish A, Levine H, Jolly MK. 2023. Low dimensionality of phenotypic space as an emergent property of coordinated teams in biological regulatory networks. bioRxiv. doi:10.1101/2023.02.03.526930.
  • Khazeem MM, Casement JW, Schlossmacher G, Kenneth NS, Sumbung NK, Chan JYT, McGow JF, Cowell IG, Austin CA. TOP2B is required to maintain the adrenergic neural phenotype and for ATRA-Induced differentiation of SH-SY5Y neuroblastoma cells. Mol Neurobiol. 2022;59(10):5987–6008. doi:10.1007/s12035-022-02949-6.
  • Van Groningen T, Akogul N, Westerhout EM, Chan A, Hasselt NE, Zwijnenburg DA, Broekmans M, Stroeken P, Haneveld F, Hooijer GKJ, et al. A NOTCH feed-forward loop drives reprogramming from adrenergic to mesenchymal state in neuroblastoma. Nat Commun. 2019;10(1). doi:10.1038/S41467-019-09470-W.
  • Forrest MP, Waite AJ, Martin-Rendon E, Blake DJ. Knockdown of human TCF4 affects multiple signaling pathways involved in cell survival, epithelial to mesenchymal transition and neuronal differentiation. PLoS ONE. 2013;8(8):e73169. doi:10.1371/JOURNAL.PONE.0073169.
  • Durbin AD, Zimmerman MW, Dharia NV, Abraham BJ, Iniguez AB, Weichert-Leahey N, He S, Krill-Burger JM, Root DE, Vazquez F, et al. Selective gene dependencies in MYCN-amplified neuroblastoma include the core transcriptional regulatory circuitry. Nat Genet. 2018;50(9):1240. doi:10.1038/S41588-018-0191-Z.
  • Tao L, Moreno‐Smith M, Ibarra‐García‐Padilla R, Milazzo G, Drolet NA, Hernandez BE, Oh YS, Patel I, Kim JJ, Zorman B, et al. CHAF1A blocks neuronal differentiation and promotes neuroblastoma oncogenesis via metabolic reprogramming. Adv Sci. 2021;8(19):2005047. doi:10.1002/advs.202005047.
  • Treiman M, Caspersen C, Christensen SB. A tool coming of age: thapsigargin as an inhibitor of sarco-endoplasmic reticulum Ca2±ATPases. Trends Pharmacol Sci. 1998;19(4):131–135. doi:10.1016/S0165-6147(98)01184-5.
  • Bensalel J, Xu H, Lu ML, Capobianco E, Wei J. RNA-seq analysis reveals significant transcriptome changes in huntingtin-null human neuroblastoma cells. BMC Med Genomics. 2021;14(1):176. doi:10.1186/S12920-021-01022-W.
  • Slade RF, Hunt DA, Pochet MM, Venema VJ, Hennigar RA. Characterization and inhibition of fatty acid synthase in pediatric tumor cell lines. Anticancer Res. 2003;23(2B):1235–1243.
  • Zirath H, Frenzel A, Oliynyk G, Segerström L, Westermark UK, Larsson K, Munksgaard Persson M, Hultenby K, Lehtiö J, Einvik C, et al. MYC inhibition induces metabolic changes leading to accumulation of lipid droplets in tumor cells. Proc Natl Acad Sci USA. 2013;110(25):10258–10263. doi:10.1073/pnas.1222404110.
  • Muralidharan S, Sehgal M, Soundharya R, Mandal S, Majumdar SS, Yeshwanth M, Saha A, Jolly MK. PD-L1 activity is associated with partial EMT and metabolic reprogramming in carcinomas. Curr Oncol. 2022;29(11):8285–8301. doi:10.3390/CURRONCOL29110654.
  • Sait S, Modak S. Anti-GD2 immunotherapy for neuroblastoma. Expert Rev Anticancer Ther. 2017;17(10):889–904. doi:10.1080/14737140.2017.1364995.
  • Mabe NW, Huang M, Dalton GN, Alexe G, Schaefer DA, Geraghty AC, Robichaud AL, Conway AS, Khalid D, Mader MM, et al. Transition to a mesenchymal state in neuroblastoma confers resistance to anti-GD2 antibody via reduced expression of ST8SIA1. Nat Cancer. 2022;3(8):976–993. doi:10.1038/s43018-022-00405-x.
  • Jansky S, Sharma AK, Körber V, Quintero A, Toprak UH, Wecht EM, Gartlgruber M, Greco A, Chomsky E, Grünewald TGP, et al. Single-cell transcriptomic analyses provide insights into the developmental origins of neuroblastoma. Nat Genet. 2021;53(5):683–693. doi:10.1038/s41588-021-00806-1.
  • Dong R, Yang R, Zhan Y, Lai H-D, Ye C-J, Yao X-Y, Luo W-Q, Cheng X-M, Miao J-J, Wang J-F, et al. Single-cell characterization of malignant phenotypes and developmental trajectories of adrenal neuroblastoma. Cancer Cell. 2020;38(5):716–733.e6. doi:10.1016/j.ccell.2020.08.014.
  • Kameneva P, Artemov AV, Kastriti ME, Faure L, Olsen TK, Otte J, Erickson A, Semsch B, Andersson ER, Ratz M, et al. Single-cell transcriptomics of human embryos identifies multiple sympathoblast lineages with potential implications for neuroblastoma origin. Nat Genet. 2021;53(5):694–706. doi:10.1038/s41588-021-00818-x.
  • Rohrer H. Linking human sympathoadrenal development and neuroblastoma. Nat Genet. 2021;53(5):593–594. doi:10.1038/s41588-021-00845-8.
  • Biedler JL, Helson L, Spengler BA. Morphology and growth, tumorigenicity, and cytogenetics of human neuroblastoma cells in continuous culture. Cancer Res. 1973;33(11):2643–2652.
  • Pasani S, Sahoo S, Jolly MK. Hybrid E/M phenotype(s) and stemness: a mechanistic connection embedded in network topology. J Clin Med. 2021;10(1):60. doi:10.1101/2020.10.18.341271.
  • Ross RA, Spengler BA. Human neuroblastoma stem cells. Semin Cancer Biol. 2007;17(3):241–247. doi:10.1016/j.semcancer.2006.04.006.