TGF-β-Induced TMEPAI Promotes Epithelial–Mesenchymal Transition in Doxorubicin-Treated Triple-Negative Breast Cancer Cells via SMAD3 and PI3K/AKT Pathway Alteration

References

• SungH, FerlayJ, SiegelRL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–249. doi:10.3322/caac.2166033538338
   PubMed Web of Science ®Google Scholar
• GuptaGK, CollierAL, LeeD, et al. Perspectives on triple-negative breast cancer: current treatment strategies, unmet needs, and potential targets for future therapies. Cancers. 2020;12:2392. doi:10.3390/cancers12092392
   PubMed Web of Science ®Google Scholar
• ReddySM, BarcenasCH, SinhaAK, et al. Long-term survival outcomes of triple-receptor negative breast cancer survivors who are disease-free at 5 years and relationship with low hormone receptor positivity. Br J Cancer. 2018;118:17–23. doi:10.1038/bjc.2017.37929235566
   PubMed Web of Science ®Google Scholar
• AliAM, AK AnsariJ, M Abd El-AzizN, et al. Triple-negative breast cancer: a tale of two decades. Anticancer Agents Med Chem. 2017;17:491–499. doi:10.2174/187152061666616072511233527456662
   PubMed Web of Science ®Google Scholar
• SharmaP. Update on the treatment of early-stage triple-negative breast cancer. Curr Treat Options Oncol. 2018;19:22. doi:10.1007/s11864-018-0539-829656345
   PubMed Web of Science ®Google Scholar
• MalhotraMK, EmensLA. The evolving management of metastatic triple-negative breast cancer. Semin Oncol. 2020;47:229–237. doi:10.1053/j.seminoncol.2020.05.00532563561
   PubMed Web of Science ®Google Scholar
• LyonsTG. Targeted therapies for triple-negative breast cancer. Curr Treat Options Oncol. 2019;20:82. doi:10.1007/s11864-019-0682-x31754897
   PubMed Web of Science ®Google Scholar
• MartinM, Ramos-MedinaR, BernatR, et al. Activity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts. Sci Rep. 2021;11:7064. doi:10.1038/s41598-021-85962-433782404
   PubMed Web of Science ®Google Scholar
• HyderT, BhattacharyaS, GadeK, NasrazadaniA, BrufskyAM. Approaching neoadjuvant therapy in the management of early-stage breast cancer. Breast Cancer. 2021;13:199–211.33833568
   PubMed Web of Science ®Google Scholar
• ChengSW, ChenPC, GerTR, ChiuHW, LinYF. GBP5 serves as a potential marker to predict a favorable response in triple-negative breast cancer patients receiving a taxane-based chemotherapy. J Pers Med. 2021;11:197. doi:10.3390/jpm1103019733809079
   PubMed Web of Science ®Google Scholar
• BlumJL, FlynnPJ, YothersG, et al. Anthracyclines in early breast cancer: the ABC trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG oncology). J Clin Oncol. 2017;35:2647–2655. doi:10.1200/JCO.2016.71.414728398846
   PubMed Web of Science ®Google Scholar
• NedeljkovićM, DamjanovićA. Mechanisms of chemotherapy resistance in triple-negative breast cancer-how we can rise to the challenge. Cells. 2019;8:957. doi:10.3390/cells8090957
   PubMed Web of Science ®Google Scholar
• GuestiniF, McNamaraKM, IshidaT, SasanoH. Triple-negative breast cancer chemosensitivity and chemoresistance: current advances in biomarkers identification. Expert Opin Ther Targets. 2016;20:705–720. doi:10.1517/14728222.2016.112546926607563
   PubMed Web of Science ®Google Scholar
• O’ReillyEA, GubbinsL, SharmaS, et al. The fate of chemoresistance in triple-negative breast cancer (TNBC). BBA Clin. 2015;3:257–275. doi:10.1016/j.bbacli.2015.03.00326676166
   PubMed Web of Science ®Google Scholar
• XuX, ZhangL, HeX, et al. TGF-β plays a vital role in triple-negative breast cancer (TNBC) drug-resistance through regulating stemness, EMT, and apoptosis. Biochem Biophys Res Commun. 2018;502:160–165. doi:10.1016/j.bbrc.2018.05.13929792857
   PubMed Web of Science ®Google Scholar
• WardhaniBW, PuteriMU, WatanabeY, LouisaM, SetiabudyR, KatoM. TGF-β-induced TMEPAI attenuates the response of triple-negative breast cancer cells to doxorubicin and paclitaxel. J Exp Pharmacol. 2020;12:17–26. doi:10.2147/JEP.S23523332158279
   PubMedGoogle Scholar
• SinghaPK, YehIT, VenkatachalamMA, SaikumarP. Transforming growth factor-beta (TGF-beta)-inducible gene TMEPAI converts TGF-beta from a tumor suppressor to a tumor promoter in breast cancer. Cancer Res. 2010;70:6377–6383. doi:10.1158/0008-5472.CAN-10-118020610632
   PubMed Web of Science ®Google Scholar
• NieZ, WangC, ZhouZ, ChenC, LiuR, WangD. Transforming growth factor-beta increases breast cancer stem cell population partially through upregulating PMEPA1 expression. Acta Biochim Biophys Sin. 2016;48:194–201. doi:10.1093/abbs/gmv13026758191
   PubMedGoogle Scholar
• WatanabeY, ItohS, GotoT, et al. TMEPAI, a transmembrane TGF-beta-inducible protein, sequesters Smad proteins from active participation in TGF-beta signaling. Mol Cell. 2010;37:123–134. doi:10.1016/j.molcel.2009.10.02820129061
   PubMed Web of Science ®Google Scholar
• ItohS, ItohF. TMEPAI family: involvement in regulation of multiple signaling pathways. J Biochem. 2018;164:195–204. doi:10.1093/jb/mvy05929945215
   PubMed Web of Science ®Google Scholar
• SinghaPK, PandeswaraS, GengH, LanR, VenkatachalamMA, SaikumarP. TGF-β induced TMEPAI/PMEPA1 inhibits canonical Smad signaling through R-Smad sequestration and promotes non-canonical PI3K/Akt signaling by reducing PTEN in triple-negative breast cancer. Genes Cancer. 2014;5:320–336. doi:10.18632/genesandcancer.3025352949
   PubMedGoogle Scholar
• ParamitaP, WardhaniBWK, WanandiSI, LouisaM. Curcumin for the prevention of epithelial-mesenchymal transition in endoxifen-treated MCF-7 breast cancer cell. Asian Pac J Cancer Prev. 2018;19:1243–1249.29801408
   PubMedGoogle Scholar
• WardhaniBW, PuteriMU, WatanabeY, LouisaM, SetiabudyR, KatoM. TMEPAI genome editing in triple-negative breast cancer cells. Med J Indones. 2017;26:14–18. doi:10.13181/mji.v26i1.1871
   Web of Science ®Google Scholar
• WardhaniBW, PuteriMU, WatanabeY, LouisaM, SetiabudyR, KatoM. Knock-out transmembrane prostate androgen-induced protein gene suppressed triple-negative breast cancer cell proliferation. Med J Indones. 2017;26:178–182. doi:10.13181/mji.v26i3.1823
   Web of Science ®Google Scholar
• DaiL, WangG, PanW. Andrographolide inhibits proliferation and metastasis of SGC7901 gastric cancer cells. BioMed Res Int. 2017;2017:6242103. doi:10.1155/2017/624210328194420
   PubMed Web of Science ®Google Scholar
• von MaltzanK, LiY, RundhaugJE, HudsonLG, FischerSM, KusewittDF. Role of the slug transcription factor in chemically-induced skin cancer. J Clin Med. 2016;5:21. doi:10.3390/jcm5020021
   Web of Science ®Google Scholar
• DaiX, AhnKS, WangLZ, et al. Ascochlorin enhances the sensitivity of doxorubicin leading to the reversal of epithelial-to-mesenchymal transition in hepatocellular carcinoma. Mol Cancer Ther. 2016;15:2966–2976. doi:10.1158/1535-7163.MCT-16-039127765853
   PubMed Web of Science ®Google Scholar
• HertantoR, BastianW, ParamitaLM. The modulation of drug efflux transporter by curcumin in MCF 7 breast cancer cells after repeated exposure of endoxifen and estradiol. Int J Appl Pharmaceut. 2018;10:102–105. doi:10.22159/ijap.2018.v10s1.21
   Google Scholar
• PuteriMU, WatanabeY, WardhaniBW, AmaliaR, AbdelazizM, KatoM. PMEPA1/TMEPAI isoforms function via its PY and Smad‐interaction motifs for tumorigenic activities of breast cancer cells. Genes Cells. 2020;25:375–390. doi:10.1111/gtc.1276632181976
   PubMed Web of Science ®Google Scholar
• CichonMA, RadiskyDC. Cutting the brakes and flooring the gas: how TMEPAI turns TGF-β into a tumor promoter. Genes Cancer. 2014;5:303. doi:10.18632/genesandcancer.3425352947
   PubMedGoogle Scholar
• BrunenD, WillemsSM, KellnerU, MidgleyR, SimonI, BernardsR. TGF-β: an emerging player in drug resistance. Cell Cycle. 2013;12:2960–2968. doi:10.4161/cc.2603423974105
   PubMed Web of Science ®Google Scholar
• OshimoriN, OristianD, FuchsE. TGF-β promotes heterogeneity and drug resistance in squamous cell carcinoma. Cell. 2015;160:963–976. doi:10.1016/j.cell.2015.01.04325723170
   PubMed Web of Science ®Google Scholar
• KatayamaH, TsouP, KobayashiM, et al. A plasma protein-derived TGFβ signature is a prognostic indicator in triple-negative breast cancer. NPJ Precis Oncol. 2019;3:1–8. doi:10.1038/s41698-019-0082-530623031
   PubMed Web of Science ®Google Scholar
• DingMJ, SuK, CuiGZ, et al. Association between transforming growth factor-β1 expression and the clinical features of triple-negative breast cancer. Oncol Lett. 2016;11:4040–4044. doi:10.3892/ol.2016.449727313737
   PubMed Web of Science ®Google Scholar
• WardhaniBWK, PuteriMU, WatanabeY, LouisaM, SetiabudyR, KatoM. Decreased sensitivity of several anticancer drugs in TMEPAI knock-out triple-negative breast cancer cells. Med J Indones. 2019;28:110–115. doi:10.13181/mji.v28i2.2687
   Web of Science ®Google Scholar
• AmaliaR, AbdelazizM, PuteriMU, et al. TMEPAI/PMEPA1 inhibits Wnt signaling by regulating β-catenin stability and nuclear accumulation in triple negative breast cancer cells. Cell Signal. 2019;59:24–33. doi:10.1016/j.cellsig.2019.03.01630890370
   PubMed Web of Science ®Google Scholar
• ImamuraY, MukoharaT, ShimonoY, et al. Comparison of 2D-and 3D-culture models as drug-testing platforms in breast cancer. Oncol Rep. 2015;33:1837–1843. doi:10.3892/or.2015.376725634491
   PubMed Web of Science ®Google Scholar
• YongKMA, UlintzPJ, CaceresS, et al. Heterogeneity at the invasion front of triple-negative breast cancer cells. Sci Rep. 2020;10:1–9.31913322
   PubMed Web of Science ®Google Scholar
• ZhuX, ChenL, HuangB, et al. The prognostic and predictive potential of Ki-67 in triple-negative breast cancer. Sci Rep. 2020;10:1–10.31913322
   PubMed Web of Science ®Google Scholar
• ZiaeiE, SaghaeidehkordiA, DillC, MaslennikovI, ChenS, KaurK. Targeting triple-negative breast cancer cells with novel cytotoxic peptide–doxorubicin conjugates. Bioconjugate Chem. 2019;30:3098–3106. doi:10.1021/acs.bioconjchem.9b00755
   PubMed Web of Science ®Google Scholar
• HsiehT, WuJ. Novel insights on the use of doxorubicin to treat chemoresistant TNBC by Immunotherapy. Int J Immunother Cancer Res. 2020;6:016–018.
   Google Scholar
• WeiL, SurmaM, GoughG, et al. Dissecting the mechanisms of doxorubicin and oxidative stress-induced cytotoxicity: the involvement of actin cytoskeleton and ROCK1. PLoS One. 2015;10:e0131763. doi:10.1371/journal.pone.013176326134406
   PubMed Web of Science ®Google Scholar
• SharifiS, BararJ, HejaziMS, SamadiN. Doxorubicin changes Bax/Bcl-xL ratio, caspase-8 and 9 in breast cancer cells. Adv Pharmaceut Bull. 2015;5:351. doi:10.15171/apb.2015.049
   PubMed Web of Science ®Google Scholar
• DuY, LiuY, XuY, et al. The transmembrane protein TMEPAI induces myeloma cell apoptosis by promoting degradation of the c-Maf transcription factor. J Biol Chem. 2018;293:5847–5859. doi:10.1074/jbc.RA117.00097229467225
   PubMed Web of Science ®Google Scholar
• VoNT, WatanabeY, ShibaA, NoguchiM, ItohS, KatoM. TMEPAI/PMEPA1 enhances tumorigenic activities in lung cancer cells. Cancer Sci. 2014;105:334. doi:10.1111/cas.1235524438557
   PubMed Web of Science ®Google Scholar
• FilyakY, FilyakO, SouchelnytskyiS, StoikaR. Doxorubicin inhibits TGF-β signaling in human lung carcinoma A549 cells. Eur J Pharmacol. 2008;590:67–73. doi:10.1016/j.ejphar.2008.05.03018606404
   PubMed Web of Science ®Google Scholar
• LuoS, YangM, LvD, et al. TMEPAI increases lysosome stability and promotes autophagy. Int J Biochem Cell Biol. 2016;76:98–106. doi:10.1016/j.biocel.2016.05.00427163528
   PubMed Web of Science ®Google Scholar
• ZhangJ, TianXJ, ZhangH, et al. TGF-β–induced epithelial-to-mesenchymal transition proceeds through stepwise activation of multiple feedback loops. Sci Signal. 2014;7:ra91. doi:10.1126/scisignal.200530425270257
   PubMed Web of Science ®Google Scholar
• WangY, LiuJ, YingX, LinPC, ZhouBP. Twist-mediated epithelial-mesenchymal transition promotes breast tumor cell invasion via inhibition of hippo pathway. Sci Rep. 2016;6:1–10.28442746
   PubMed Web of Science ®Google Scholar
• SinghaPK, PandeswaraS, GengH, et al. Increased Smad3, and reduced Smad2 levels mediate the functional switch of TGF-β from growth suppressor to growth and metastasis promoter through TMEPAI/PMEPA1 in triple-negative breast cancer. Genes Cancer. 2019;10:134–149. doi:10.18632/genesandcancer.19431798766
   PubMedGoogle Scholar
• WendtMK, AllingtonTM, SchiemannWP. Mechanisms of the epithelial-mesenchymal transition by TGF-β. Future Oncol. 2009;5:1145–1168. doi:10.2217/fon.09.9019852727
   PubMed Web of Science ®Google Scholar
• HanRF, JiX, DongXG, et al. An epigenetic mechanism underlying doxorubicin-induced EMT in the human BGC-823 gastric cancer cell. Asian Pac J Cancer Prev. 2014;15:4271–4274. doi:10.7314/APJCP.2014.15.10.427124935383
   PubMedGoogle Scholar
• DuB, ShimJS. Targeting epithelial-mesenchymal transition (EMT) to overcome drug resistance in cancer. Molecules. 2016;21:965. doi:10.3390/molecules21070965
   PubMed Web of Science ®Google Scholar
• ZhangL, WangX, LaiC, ZhangH, LaiM. PMEPA1 induces EMT via non‐canonical TGF‐β signaling in colorectal cancer. J Cell Mol Med. 2019;23:3603–3615. doi:10.1111/jcmm.1426130887697
   PubMed Web of Science ®Google Scholar
• ZhengHC. The molecular mechanisms of chemoresistance in cancers. Oncotarget. 2017;8:59950.28938696
   PubMed Web of Science ®Google Scholar
• TakanoM, YamamotoC, YamaguchiK, KawamiM, YumotoR. Analysis of TGF-β1- and drug-induced epithelial-mesenchymal transition in cultured alveolar epithelial cell line RLE/Abca3. Drug Metab Pharmacokinet. 2015;30:111–118. doi:10.1016/j.dmpk.2014.10.00725760538
   PubMed Web of Science ®Google Scholar
• SaxenaM, StephensMA, PathakH, RangarajanA. Transcription factors that mediate epithelial-mesenchymal transition lead to multidrug resistance by upregulating ABC transporters. Cell Death Dis. 2011;2:e179. doi:10.1038/cddis.2011.6121734725
   PubMed Web of Science ®Google Scholar
• JiangZS, SunYZ, WangSM, RuanJS. Epithelial-mesenchymal transition: a potential regulator of ABC transporters in tumor progression. J Cancer. 2017;8:2319–2327. doi:10.7150/jca.1907928819436
   PubMed Web of Science ®Google Scholar
• TsouSH, ChenTM, HsiaoHT, ChenYH. A critical dose of doxorubicin is required to alter the gene expression profiles in MCF-7 cells acquiring multidrug resistance. PLoS One. 2015;10:e0116747. doi:10.1371/journal.pone.011674725635866
   PubMed Web of Science ®Google Scholar