Artikel Review: Interaksi Silang Pensinyalan Wnt dan TGF-β pada Kanker Prostat

Luthfi H. Siwi; Imam A. Wicaksono; Riezki Amalia

doi:10.15416/ijcp.2020.9.4.341

Artikel Review: Interaksi Silang Pensinyalan Wnt dan TGF-β pada Kanker Prostat

Luthfi H. Siwi, Imam A. Wicaksono, Riezki Amalia

Abstract

Pertumbuhan dan perkembangan kanker dapat dipengaruhi oleh perubahan jalur pensinyalan. Dua pensinyalan utama yang mengalami perubahan pada kanker adalah pensinyalan Wnt dan TGF-β. Pensinyalan Wnt memiliki peran dalam proliferasi dan apoptosis sel, sedangkan pensinyalan TGF-β memiliki peran dalam menghambat pertumbuhan dan perkembangan tumor. Interaksi silang kedua pensinyalan ini berhubungan dengan perkembangan dan pertumbuhan sel kanker, termasuk kanker prostat. Artikel ini membahas peran pensinyalan Wnt dan TGF-β, serta interaksi silang antara keduanya pada kanker prostat. Kajian pustaka ini membahas peran pensinyalan Wnt dan TGF-β, serta interaksi silang antara keduanya pada kanker prostat. Kajian dilakukan terhadap 30 artikel yang didapatkan melalui pencarian artikel dengan kata kunci “Prostate cancer, Signaling pathways, Wnt in prostate cancer, TGF-β in prostate cancer, Crosstalk between TGF-β and Wnt in prostate cancer, TCF/LEF and β-catenin, TGF-β in cancer, Androgen Receptor Wnt Prostate Cancer, Androgen Receptor TGF-β Prostate Cancer”. Sebagai simpulan bahwa interaksi silang antara Wnt dan TGF-β pada kanker prostat terjadi pada jalur kanonik dan non kanonik dengan beberapa protein yang terlibat pada kedua pensinyalan tersebut serta dapat dimediasi oleh beberapa pensinyalan lain seperti PI3K, RAS/MAPK dan AR. Interaksi silang pensinyalan Wnt dan TGF-β berperan penting dalam perkembangan dan progresi kanker prostat, dan kajian pustaka ini diharapkan dapat menjadi dasar pengembangan terapeutik tertarget pada kanker prostat.

Kata kunci: Reseptor androgen, interaksi silang, kanker prostat, pensinyalan TGF-β, pensinyalan Wnt

Review Article: Crosstalk Between Wnt And TGF-β Signaling in Prostate Cancer

Abstract

The growth and development of cancer is capable of impact by signaling pathways changes, including the WNT and TGF-β primary signaling. Furthermore, WNT signaling influences cell proliferation and apoptosis, while TGF-β inhibits tumors progress and advancement, and the cross-interaction of both signaling is associated with expansion of tumor cells, including prostate cancer. This literature study explores the role of WNT and TGF-β signaling, and relationship between the two in prostate cancer. The method employed included search for articles with the keywords “Prostate cancer, Signaling pathways, WNT in Prostate cancer, TGF-β in Prostate cancer, Crosstalk between TGF-β and Wnt in Prostate cancer, TCF/LEF and β-catenin, TGF-β in cancer, Androgen Receptor WNT Prostate Cancer, Androgen Receptor TGF-β Prostate Cancer”. Also, 30 of the 459 articles employed in this research revealed Wnt signaling, TGF-β and the connection with prostate cancer. The results indicated crosstalk between Wnt and TGF-β in prostate cancer occurs in the canonical and noncanonical pathways with some involved proteins, and is capable of mediation by other signaling including PI3K, RAS/MAPK and AR. Also, the crosstalk of Wnt and TGF-β signaling is significant in the growth and progression of prostate cancer, therefore this study is anticipated as the foundation of targeted prostate cancer therapeutic development.

Keywords: Androgen receptor, crosstalk, prostate cancer, TGF-β signaling, Wnt signaling

Keywords

Reseptor androgen, interaksi silang, kanker prostat, pensinyalan TGF-β, pensinyalan Wnt

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References

World Health Organization. Cancer. [Diakses pada: 6 March 2020]. Tersedia dari: https://www.who.int/health-topics/cancer#tab=tab_1

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. doi: 10.3322/caac.21492

Pusat Data dan Informasi Kementerian Kesehatan Republik Indonesia. Situasi penyakit kanker. 2018. Jakarta Selatan: Kementerian Kesehatan Republik Indonesia; 2018.

Amalia R, Abdelaziz M, Puteri MU, Hwang J, Anwar F, Watanabe Y, 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.2019.03.016

Li R, Quan Y, Xia W. SIRT3 inhibits prostate cancer metastasis through regulation of FOXO3A by suppressing Wnt/β-catenin pathway. Exp Cell Res. 2018;364(2):143–51. doi: 10.1016/j.yexcr.2018.01.036

Murillo-Garzón V, Kypta R. WNT signalling in prostate cancer. Nat Rev Urol. 2017;14(11):683–96. doi: 10.1038/nrurol.2017.144

Anastas JN, Moon RT. WNT signalling pathways as therapeutic targets in cancer. Nat Rev Cancer. 2013;13(1):11–26. doi: 10.1038/nrc3419

Cao Z, Kyprianou N. Mechanisms navigating the TGF-B pathway in prostate cancer. Asian J Urol. 2015;2(1):11–8. doi: 10.1016/j.ajur.2015.04.011

Ahel J, Hudorović N, Vičić-Hudorović V, Nikles H. TGF-beta in the natural history of prostate cancer. Acta Clin Croat. 2019;58(1):128–38. doi: 10.20471/acc.2019.58.01.17

Sanchez-Vega F, Mina M, Armenia J, Chatila WK, Luna A, La KC, et al. Oncogenic signaling pathways in the cancer genome atlas. Cell. 2018;173(2):321-73. doi: 10.1016/j.cell.2018.03.035

Schneider JA, Logan SK. Revisiting the role of Wnt/β-catenin signaling in prostate cancer. Mol Cell Endocrinol. 2018;462(Pt A):3–8. doi: 10.1016/j.mce.2017.02.008

Pelullo M, Zema S, Nardozza F, Checquolo S, Screpanti I, Bellavia D. Wnt, Notch, and TGF-β Pathways Impinge on Hedgehog Signaling Complexity: An Open Window on Cancer. Front Genet. 2019;10:711. doi: 10.3389/fgene.2019.00711

Luo K. Signaling cross talk between TGF-β/Smad and other signaling pathways. Cold Spring Harb Persepctives Biol. 2017;9(1):a022137. doi: 10.1101/cshperspect.a022137

Murillo-Garzón V, Gorroño-Etxebarria I, Åkerfelt M, Puustinen MC, Sistonen L, Nees M, et al. Frizzled-8 integrates Wnt-11 and transforming growth factor-β signaling in prostate cancer. Nat Commun. 2018;9(1):1747. doi: 10.1038/s41467-018-04042-w

Fujita K, Nonomura N. Role of androgen receptor in prostate cancer: A review. World J Mens Health. 2019;37(3):288-95. doi: 10.5534/wjmh.180040

Tindall D, Lonergan P. Androgen receptor signaling in prostate cancer development and progression. J Carcinog. 2011;10(1):20. doi: 10.4103/1477-3163.83937

Karantanos T, Corn PG, Thompson TC. Prostate cancer progression after androgen deprivation therapy: mechanisms of castrate resistance and novel therapeutic approaches. Oncogene. 2013;32(49):5501–11. doi: 10.1038/onc.2013.206

Humphrey PA. Histopathology of prostate cancer. Cold Spring Harb Perspect Med. 2017;7(10):a030411. doi: 10.1101/cshperspect.a030411

Jung ME, Ouk S, Yoo D, Sawyers CL, Chen C, Tran C, et al. Structure-activity relationship for thiohydantoin androgen receptor antagonists for castration-resistant prostate cancer (CRPC). J Med Chem. 2010;53(7):2779–96. doi: 10.1021/jm901488g

Malinowski B, Wiciński M, Musiała N, Osowska I, Szostak M. Previous, current, and future pharmacotherapy and diagnosis of prostate cancer. A Comprehensive Review. Diagnostics. 2019;9(4):161. doi: 10.3390/diagnostics9040161

Nair A, Chauhan P, Saha B, Kubatzky KF. Conceptual evolution of cell signaling. Int J Mol Sci. 2019;20(13):3292. doi: 10.3390/ijms20133292

Nusse R, Clevers H. Wnt/β-Catenin signaling, disease, and emerging therapeutic modalities. Cell. 2017. 169(6):985–99. doi: 10.1016/j.cell.2017.05.016

MacDonald BT, He X. Frizzled and LRP5/6 receptors for Wnt/β-catenin signaling. Cold Spring Harb Perspect Biol. 2012;4(12):a007880–a007880. doi: 10.1101/cshperspect.a007880

Janda CY, Waghray D, Levin AM, Thomas C, Garcia KC. Structural basis of Wnt recognition by frizzled. Science. 2012;337(6090):59–64. doi: 10.1126/science.1222879

Tauriello DVF, Jordens I, Kirchner K, Slootstra JW, Kruitwagen T, Bouwman BAM, et al. Wnt/β-catenin signaling requires interaction of the Dishevelled DEP domain and C terminus with a discontinuous motif in Frizzled. Proc Natl Acad Sci USA. 2012;109(14):5154–5. doi: 10.1073/pnas.1114802109

Krishnamurthy N, Kurzrock R. Targeting the Wnt/beta-catenin pathway in cancer: Update on effectors and inhibitors. Cancer Treat Rev. 2018;62:50–60. doi: 10.1016/j.ctrv.2017.11.002

van Amerongen R. Alternative Wnt pathways and receptors. Cold Spring Harb Perspect Biol. 2012;4(10): a007914. doi: 10.1101/cshperspect.a007914

Uysal-Onganer P, Kawano Y, Caro M, Walker MM, Diez S, Darrington RS, et al. Wnt-11 promotes neuroendocrine-like differentiation, survival and migration of prostate cancer cells. Mol Cancer. 2010;9:55. doi: 10.1186/1476-4598-9-55

Uysal-Onganer P, Kypta RM. Wnt11 in 2011-the regulation and function of a non-canonical Wnt. Acta Physiol. 2012;204(1):52–64. doi: 10.1111/j.1748-1716.2011.02297.x

Volante M, Tota D, Giorcelli J, Bollito E, Napoli F, Vatrano S, et al. Androgen deprivation modulates gene expression profile along prostate cancer progression. Hum Pathol. 2016;56:81–8. doi: 10.1016/j.humpath.2016.06.004

Li Z, Xu Z, Duan C, Liu W, Sun J, Han B. Role of TCF/LEF transcription factors in bone development and osteogenesis. Int J Med Sci. 2018;15(12):1415–22. doi: 10.7150/ijms.26741

Wu L, Zhao JC, Kim J, Jin HJ, Wang CY, Yu J. ERG is a critical regulator of Wnt/LEF1 signaling in prostate cancer. Cancer Res. 2013;73(19):6068-79. doi: 10.1158/0008-5472.CAN-13-0882

Bauman TM, Vezina CM, Ricke EA, Halberg RB, Huang W, Peterson RE, et al. Expression and colocalization of β-catenin and lymphoid enhancing factor-1 in prostate cancer progression. Hum Pathol. 2016;51:124–33. doi: 10.1016/j.humpath.2015.12.024

Kypta RM, Waxman J. Wnt/β-catenin signalling in prostate cancer. Nat Rev Urol. 2012;9(8):418–28. doi: 10.1038/nrurol.2012.116

Massagué J. TGFβ signalling in context. Nat Rev Mol Cell Biol. 2012;13(10):616–30. doi: 10.1038/nrm3434

Morikawa M, Derynck R, Miyazono K. TGF- β and the TGF-β family: Context-dependent roles in cell and tissue physiology. Cold Spring Harb Perspect Biol. 2016;8(5):a021873. doi: 10.1101/cshperspect.a021873

Vander Ark A, Cao J, Li X. TGF-β receptors: In and beyond TGF-β signaling. Cell Signal. 2018;52:112–20. doi: 10.1016/j.cellsig.2018.09.002

Fei T, Xia K, Li Z, Zhou B, Zhu S, Chen H, et al. Genome-wide mapping of SMAD target genes reveals the role of BMP signaling in embryonic stem cell fate determination. Genome Res. 2010;20(1):36–44. doi: 10.1101/gr.092114.109

Chen X-F, Zhang H-J, Wang H-B, Zhu J, Zhou W-Y, Zhang H, et al. Transforming growth factor-β1 induces epithelial-to-mesenchymal transition in human lung cancer cells via PI3K/Akt and MEK/Erk1/2 signaling pathways. Mol Biol Rep. 2012;39(4):3549–56. doi: 10.1007/s11033-011-1128-0

Korol A, Taiyab A, West-Mays JA. RhoA/ROCK signaling regulates TGFβ-induced epithelial-mesenchymal transition of lens epithelial cells through MRTF-A. Mol Med. 2016;22(1):713–23. doi: 10.2119/molmed.2016.00041

Vo BT, Morton D, Komaragiri S, Millena AC, Leath C, Khan SA. TGF-β effects on prostate cancer cell migration and invasion are mediated by PGE2 through activation of PI3K/AKT/mTOR pathway. Endocrinology. 2013;154(5):1768–79. doi: 10.1210/en.2012-2074

Jones E, Pu H, Kyprianou N. Targeting TGF-β in prostate cancer: Therapeutic possibilities during tumor progression. Expert Opin Ther Targets. 2009;13(2)227-34. doi: 10.1517/14728220802705696

Tindall DJ. Prostate cancer: Biochemistry, molecular biology and genetics. J Carcinogenesis. 2013;1–522 doi: 10.1007/978-1-4614-6828-8

Kjolby RAS, Harland RM. Genome-wide identification of Wnt/β-catenin transcriptional targets during Xenopus gastrulation. Dev Biol. 2017;426(2):165–75. doi: 10.1016/j.ydbio.2016.03.021

Zinski J, Tajer B, Mullins MC. TGF-β family signaling in early vertebrate development. Cold Spring Harb Perspect Biol. 2018;10(6):a033274. doi: 10.1101/cshperspect.a033274

Zhang M, Wang M, Tan X, Li TF, Zhang YE, Chen D. Smad3 prevents β-catenin degradation and facilitates β-catenin nuclear translocation in chondrocytes. J Biol Chem. 2010;285(12):8703–10.. doi: 10.1074/jbc.M109.093526

Zhou S. TGF-β regulates β-catenin signaling and osteoblast differentiation in human mesenchymal stem cells. J Cell Biochem. 2011;112(6):1651–60. doi: 10.1002/jcb.23079

Attisano L, Wrana JL. Signal integration in TGF-β, WNT, and Hippo pathways. F1000Prime Rep. 2013;5:17. doi: 10.12703/P5-17

Mandel A, Larsson P, Sarwar M, Semenas J, Syed Khaja AS, Persson JL. The interplay between AR, EGF receptor and MMP-9 signaling pathways in invasive prostate cancer. Mol Med. 2018;24(1):34. doi: 10.1186/s10020-018-0035-4

Zhan T, Rindtorff N, Boutros M. Wnt signaling in cancer. Oncogene. 2017;36(11):1461–73. doi: 10.1038/onc.2016.304

Freese JL, Pino D, Pleasure SJ. Wnt signaling in development and disease. Neurobiol Dis. 2010;38(2):148–53. doi: 10.1016/j.nbd.2009.09.003

Cheruku HR, Mohamedali A, Cantor DI, Tan SH, Nice EC, Baker MS. Transforming growth factor-β, MAPK and Wnt signaling interactions in colorectal cancer. EuPA Open Proteomics. 2015;8:104–15. doi: 10.1016/j.euprot.2015.06.004

Beltran H, Yelensky R, Frampton GM, Park K, Downing SR, MacDonald TY, et al. Targeted next-generation sequencing of advanced prostate cancer identifies potential therapeutic targets and disease heterogeneity. Eur Urol. 2013;63(5):920–6. doi: 10.1016/j.eururo.2012.08.053

Grasso CS, Wu Y, Robinson DR, Cao X, Dhanasekaran SM, Khan AP, et al. The mutational landscape of lethal castration-resistant prostate cancer. Nature. 2012;487(7406):239–43. doi: 10.1038/nature11125

Robinson D, Van Allen EM, Wu Y-M, Schultz N, Lonigro RJ, Mosquera J-M, et al. Integrative clinical genomics of advanced prostate cancer. Cell. 2015;162(2):454. doi: 10.1016/j.cell.2015.06.053

Chen C-L, Mahalingam D, Osmulski P, Jadhav RR, Wang C-M, Leach RJ, et al. Single-cell analysis of circulating tumor cells identifies cumulative expression patterns of EMT-related genes in metastatic prostate cancer. Prostate. 2013;73(8):813–26. doi: 10.1002/pros.22625

Miyamoto DT, Zheng Y, Wittner BS, Lee RJ, Zhu H, Broderick KT, et al. RNA-Seq of single prostate CTCs implicates noncanonical Wnt signaling in antiandrogen resistance. Science. 2015;349(6254):1351–6. doi: 10.1126/science.aab0917

Sandsmark E, Hansen AF, Selnæs KM, Bertilsson H, Bofin AM, Wright AJ, et al. A novel non-canonical Wnt signature for prostate cancer aggressiveness. Oncotarget. 2017;8(6):9572–86. doi: 10.18632/oncotarget.14161

Gupta S, Iljin K, Sara H, Mpindi JP, Mirtti T, Vainio P, et al. FZD4 as a mediator of ERG oncogene-induced WNT signaling and epithelial-to-mesenchymal transition in human prostate cancer cells. Cancer Res. 2010;70(17):6735–45. doi: 10.1158/0008-5472.CAN-10-0244

Zhang S, Chen L, Wang-Rodriguez J, Zhang L, Cui B, Frankel W, et al. The onco-embryonic antigen ROR1 is expressed by a variety of human cancers. Am J Pathol. 2012;181(6):1903–10. doi: 10.1016/j.ajpath.2012.08.024

Thiele S, Rauner M, Goettsch C, Rachner TD, Benad P, Fuessel S, et al. Expression profile of WNT molecules in prostate cancer and its regulation by aminobisphosphonates. J Cell Biochem. 2011;112(6):1593–600. doi: 10.1002/jcb.23070

Kumon H, Ariyoshi Y, Sasaki K, Sadahira T, Araki M, Ebara S, et al. Adenovirus vector carrying REIC/DKK-3 gene: neoadjuvant intraprostatic injection for high-risk localized prostate cancer undergoing radical prostatectomy. Cancer Gene Ther. 2016;23(11):400–9. doi: 10.1038/cgt.2016.53

Xu W, Zeng F, Li S, Li G, Lai X, Wang QJ, et al. Crosstalk of protein kinase C ε with Smad2/3 promotes tumor cell proliferation in prostate cancer cells by enhancing aerobic glycolysis. Cell Mol Life Sci. 2018;75(24):4583–98. doi: 10.1007/s00018-018-2914-9

Garg R, Benedetti LG, Abera MB, Wang H, Abba M, Kazanietz MG. Protein kinase C and cancer: What we know and what we do not. Oncogene. 2014;33(45):5225–37. doi: 10.1038/onc.2013.524

Dupasquier S, Blache P, Picque Lasorsa L, Zhao H, Abraham J-D, Haigh JJ, et al. Modulating PKCα Activity to Target Wnt/β-Catenin Signaling in Colon Cancer. Cancers. 2019;11(5):693. doi: 10.3390/cancers11050693

Khurana N, Sikka SC. Interplay between SOX9, Wnt/β-catenin and androgen receptor signaling in castration-resistant prostate cancer. Int J Mol Sci. 2019;20(9):2066. doi: 10.3390/ijms20092066

Chavez RD, Coricor G, Perez J, Seo H-S, Serra R. SOX9 protein is stabilized by TGF-β and regulates PAPSS2 mRNA expression in chondrocytes. Osteoarthr Cartil. 2017;25(2):332–40. doi: 10.1016/j.joca.2016.10.007

Lee M, Lee J, Kim Y, Lee H. The metastasis suppressor CD82/KAI1 represses the TGF-β 1 and Wnt signalings inducing epithelial-to-mesenchymal transition linked to invasiveness of prostate cancer cells. Prostate. 2019;79(12):1394–405. doi: 10.1002/pros.23837

Moreno CS. The sex-determining region Y-box 4 and homeobox C6 transcriptional networks in prostate cancer progression. Am J Pathol. 2010;176(2):518–27. doi: 10.2353/ajpath.2010.090657

Lin S-R, Mokgautsi N, Liu Y-N. Ras and Wnt interaction contribute in prostate csncer bone metastasis. Molecules. 2020;25(10):2380. doi: 10.3390/molecules25102380

Browne AJ, Göbel A, Thiele S, Hofbauer LC, Rauner M, Rachner TD. p38 MAPK regulates the Wnt inhibitor Dickkopf-1 in osteotropic prostate cancer cells. Cell Death Dis. 2016;7(2):e2119–e2119. doi: 10.1038/cddis.2016.32

Ekman M, Mu Y, Lee SY, Edlund S, Kozakai T, Thakur N, et al. APC and Smad7 link TGFβ type I receptors to the microtubule system to promote cell migration. Mol Biol Cell. 2012;23(11):2109–21. doi: 10.1091/mbc.e10-12-1000