Login Register Cart 0
Generic placeholder image

Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Mini-Review Article

Targeting the Transforming Growth Factor-beta Signaling Pathway in the Treatment of Gynecologic Cancer

Author(s): Sadaf Ghanaatgar-Kasbi, Farzaneh Pouya, Negar Khoshghamat, Ghazaleh Ghorbannezhad, Majid Khazaei, Malihe Hasanzadeh, Gordon A. Ferns and Amir Avan*

Volume 23, Issue 1, 2023

Published on: 05 September, 2022

Page: [15 - 24] Pages: 10

DOI: 10.2174/1568009622666220623115614

Price: $65

Abstract

The transforming growth factor-beta (TGF-β) signaling pathway has been reported to be dysregulated in the pathogenesis of several malignancies, including gynecologic cancers. This provides proof of concept of its potential value as a therapeutic target and prognostic biomarker in cervical cancer. Here we provide an overview of the biological role and clinical impact of TGF-β inhibitors either as a single agent or as a combinatorial therapy in gynecological cancers, concentrating on phase I to phase II/III clinical trials. Aberrant TGF-β signaling may lead to carcinogenesis. Inhibition of TGF-β represents an interesting area of focus for the treatment of gynecological cancer. Several TGF-β inhibitors are potential anticancer agents and are undergoing clinical trials in cancer, including galunisertib, dalantercept, and vigil. There is a growing body of data showing the potential therapeutic impact of targeting the TGF-β pathway in different cancer types, although further studies are still warranted to explore the value of this strategy and finding the most appropriate patients who could most benefit from therapy.

Keywords: TGF-β pathway, TGF-β inhibitors, gynecologic cancer, target therapy, anticancer agents, malignancies.

« Previous Next »
[1]
Miller, K.D.; Nogueira, L.; Mariotto, A.B.; Rowland, J.H.; Yabroff, K.R.; Alfano, C.M.; Jemal, A.; Kramer, J.L.; Siegel, R.L. Cancer treatment and survivorship statistics. CA Cancer J. Clin., 2019, 69(5), 363-385.
[http://dx.doi.org/10.3322/caac.21565] [PMID: 31184787]
[2]
Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer Statistics, 2021. CA Cancer J. Clin., 2021, 71(1), 7-33.
[http://dx.doi.org/10.3322/caac.21654] [PMID: 33433946]
[3]
Cassedy, H.F.; Tucker, C.; Hynan, L.S.; Phillips, R.; Adams, C.; Zimmerman, M.R. Frequency of psychological distress in gynecologic cancer patients seen in a large urban medical center. Bayl. Uni. Med. Cent. Proc., 2018, 31(20), 161-164.
[4]
Hazewinkel, M.H.; Sprangers, M.A.; Velden, J.; Burger, M.P.; Roovers, J-P.W. Severe pelvic floor symptoms after cervical cancer treatment are predominantly associated with mental and physical well-being and body image: a cross-sectional study. Int. J. Gynecol. Cancer, 2012, 22(1), 154-160.
[http://dx.doi.org/10.1097/IGC.0b013e3182332df8] [PMID: 22080883]
[5]
Akhurst, R.J. Targeting TGF-β signaling for therapeutic gain. Cold Spring Harb. Perspect. Biol., 2017, 9(10), a022301.
[http://dx.doi.org/10.1101/cshperspect.a022301] [PMID: 28246179]
[6]
Ghanaatgar-Kasbi, S.; Khazaei, M.; Rastgar-Moghadam, A.; Ferns, G.A.; Hassanian, S.M.; Avan, A. The Therapeutic Potential of MEK1/2 inhibitors in the treatment of gynecological cancers: Rational strategies and recent progress. Curr. Cancer Drug Targets, 2020, 20(6), 417-428.
[http://dx.doi.org/10.2174/1568009620666200424144303] [PMID: 32329688]
[7]
Nguyen, M.L.T.; Toan, N.L.; Bozko, M.; Bui, K.C.; Bozko, P. Cholangiocarcinoma therapeutics: an update. Curr. Cancer Drug Targets, 2021, 21(6), 457-475.
[http://dx.doi.org/10.2174/1568009621666210204152028] [PMID: 33563168]
[8]
Ghanaatgar-Kasbi, S.; Khorrami, S.; Avan, A.; Aledavoud, S.A.; Ferns, G.A. Targeting the c-MET/HGF signaling pathway in pancreatic ductal adenocarcinoma. Curr. Pharm. Des., 2018, 24(39), 4619-4625.
[http://dx.doi.org/10.2174/1381612825666190110145855] [PMID: 30636579]
[9]
Shaaban, M.; Othman, H.; Ibrahim, T.; Ali, M.; Abdelmoaty, M.; Abdel-Kawi, A-R.; Mostafa, A.; El Nakeeb, A.; Emam, H.; Refaat, A. Immune checkpoint regulators: A new era toward promising cancer therapy. Curr. Cancer Drug Targets, 2020, 20(6), 429-460.
[http://dx.doi.org/10.2174/1568009620666200422081912] [PMID: 32321404]
[10]
Neuzillet, C.; Tijeras-Raballand, A.; Cohen, R.; Cros, J.; Faivre, S.; Raymond, E.; de Gramont, A. Targeting the TGFβ pathway for cancer therapy. Pharmacol. Ther., 2015, 147, 22-31.
[http://dx.doi.org/10.1016/j.pharmthera.2014.11.001] [PMID: 25444759]
[11]
Massagué, J. G1 cell-cycle control and cancer. Nature, 2004, 432(7015), 298-306.
[http://dx.doi.org/10.1038/nature03094] [PMID: 15549091]
[12]
Takekawa, M.; Tatebayashi, K.; Itoh, F.; Adachi, M.; Imai, K.; Saito, H. Smad-dependent GADD45β expression mediates delayed activa-tion of p38 MAP kinase by TGF-β. EMBO J., 2002, 21(23), 6473-6482.
[http://dx.doi.org/10.1093/emboj/cdf643] [PMID: 12456654]
[13]
Ohgushi, M.; Kuroki, S.; Fukamachi, H.; O’Reilly, L.A.; Kuida, K.; Strasser, A.; Yonehara, S. Transforming growth factor β-dependent sequential activation of Smad, Bim, and caspase-9 mediates physiological apoptosis in gastric epithelial cells. Mol. Cell. Biol., 2005, 25(22), 10017-10028.
[http://dx.doi.org/10.1128/MCB.25.22.10017-10028.2005] [PMID: 16260615]
[14]
Santibanez, JF.; Krstic, J.; Quintanilla, M.; Bernabeu, C. TGF-β signalling and its role in cancer progression and metastasis; eLS, 2016, pp. 1-9.
[15]
Beerling, E.; Seinstra, D.; de Wit, E.; Kester, L.; van der Velden, D.; Maynard, C.; Schäfer, R.; van Diest, P.; Voest, E.; van Oudenaarden, A.; Vrisekoop, N.; van Rheenen, J. Plasticity between epithelial and mesenchymal states unlinks EMT from metastasis-enhancing stem cell capacity. Cell Rep., 2016, 14(10), 2281-2288.
[http://dx.doi.org/10.1016/j.celrep.2016.02.034] [PMID: 26947068]
[16]
Zheng, X.; Carstens, J.L.; Kim, J.; Scheible, M.; Kaye, J.; Sugimoto, H.; Wu, C.C.; LeBleu, V.S.; Kalluri, R. Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature, 2015, 527(7579), 525-530.
[http://dx.doi.org/10.1038/nature16064] [PMID: 26560028]
[17]
Gachpazan, M.; Kashani, H.; Hassanian, S.M.; Khazaei, M.; Khorrami, S.; Ferns, G.A.; Avan, A. Therapeutic potential of targeting transforming growth factor-beta in colorectal cancer: rational and progress. Curr. Pharm. Des., 2019, 25(38), 4085-4089.
[http://dx.doi.org/10.2174/1381612825666191105114539] [PMID: 31692434]
[18]
Hao, Y.; Baker, D.; Ten Dijke, P. TGF-β-mediated epithelial-mesenchymal transition and cancer metastasis. Int. J. Mol. Sci., 2019, 20(11), 2767.
[http://dx.doi.org/10.3390/ijms20112767] [PMID: 31195692]
[19]
Robertson, I.B.; Rifkin, D.B. Regulation of the bioavailability of TGF-β and TGF-β-related proteins. Cold Spring Harb. Perspect. Biol., 2016, 8(6), a021907.
[http://dx.doi.org/10.1101/cshperspect.a021907] [PMID: 27252363]
[20]
Heldin, C-H.; Moustakas, A. Role of Smads in TGF-β signaling. Cell Tissue Res., 2012, 347(1), 21-36.
[http://dx.doi.org/10.1007/s00441-011-1190-x] [PMID: 21643690]
[21]
Heldin, C-H.; Miyazono, K.; ten Dijke, P. TGF-β signalling from cell membrane to nucleus through Smad proteins. Nature, 1997, 390(6659), 465-471.
[http://dx.doi.org/10.1038/37284] [PMID: 9393997]
[22]
Schmierer, B.; Hill, C.S. TGFbeta-Smad signal transduction: molecular specificity and functional flexibility. Nat. Rev. Mol. Cell Biol., 2007, 8(12), 970-982.
[http://dx.doi.org/10.1038/nrm2297] [PMID: 18000526]
[23]
Lee, M.K.; Pardoux, C.; Hall, M.C.; Lee, P.S.; Warburton, D.; Qing, J.; Smith, S.M.; Derynck, R. TGF-β activates Erk MAP kinase signal-ling through direct phosphorylation of ShcA. EMBO J., 2007, 26(17), 3957-3967.
[http://dx.doi.org/10.1038/sj.emboj.7601818] [PMID: 17673906]
[24]
Rodón, L.; Gonzàlez-Juncà, A.; Inda, M.M.; Sala-Hojman, A.; Martínez-Sáez, E.; Seoane, J. Active CREB1 promotes a malignant TGFβ2 autocrine loop in glioblastoma. Cancer Discov., 2014, 4(10), 1230-1241.
[http://dx.doi.org/10.1158/2159-8290.CD-14-0275] [PMID: 25084773]
[25]
Flanders, K.C.; Wakefield, L.M. Transforming growth factor-(β)s and mammary gland involution; functional roles and implications for cancer progression. J. Mammary Gland Biol. Neoplasia, 2009, 14(2), 131-144.
[http://dx.doi.org/10.1007/s10911-009-9122-z] [PMID: 19396528]
[26]
Samarakoon, R.; Dobberfuhl, A.D.; Cooley, C.; Overstreet, J.M.; Patel, S.; Goldschmeding, R.; Meldrum, K.K.; Higgins, P.J. Induction of renal fibrotic genes by TGF-β1 requires EGFR activation, p53 and reactive oxygen species. Cell. Signal., 2013, 25(11), 2198-2209.
[http://dx.doi.org/10.1016/j.cellsig.2013.07.007] [PMID: 23872073]
[27]
Samarakoon, R.; Higgins, P.J. Integration of non-Smad and Smad signaling in TGF-β1-induced plasminogen activator inhibitor type-1 gene expression in vascular smooth muscle cells. Thromb. Haemost., 2008, 100(6), 976-983.
[http://dx.doi.org/10.1160/TH08-05-0273] [PMID: 19132220]
[28]
Xiong, S.; Cheng, J-C.; Klausen, C.; Zhao, J.; Leung, P.C. TGF-β1 stimulates migration of type II endometrial cancer cells by down-regulating PTEN via activation of Smad and ERK1/2 signaling pathways. Oncotarget, 2016, 7(38), 61262-61272.
[http://dx.doi.org/10.18632/oncotarget.11311] [PMID: 27542208]
[29]
Yamamura, S.; Matsumura, N.; Mandai, M.; Huang, Z.; Oura, T.; Baba, T.; Hamanishi, J.; Yamaguchi, K.; Kang, H.S.; Okamoto, T.; Abiko, K.; Mori, S.; Murphy, S.K.; Konishi, I. The activated transforming growth factor-beta signaling pathway in peritoneal metastases is a potential therapeutic target in ovarian cancer. Int. J. Cancer, 2012, 130(1), 20-28.
[http://dx.doi.org/10.1002/ijc.25961] [PMID: 21503873]
[30]
Akhurst, R.J.; Hata, A. Targeting the TGFβ signalling pathway in disease. Nat. Rev. Drug Discov., 2012, 11(10), 790-811.
[http://dx.doi.org/10.1038/nrd3810] [PMID: 23000686]
[31]
He, A-D.; Wang, S-P.; Xie, W.; Song, W.; Miao, S.; Yang, R-P.; Zhu, Y.; Xiang, J.Z.; Ming, Z.Y. Platelet derived TGF-β promotes cervical carcinoma cell growth by suppressing KLF6 expression. Oncotarget, 2017, 8(50), 87174-87181.
[http://dx.doi.org/10.18632/oncotarget.19912] [PMID: 29152072]
[32]
Wang, D.; Wang, W.; Liang, Q.; He, X.; Xia, Y.; Shen, S.; Wang, H.; Gao, Q.; Wang, Y. DHEA-induced ovarian hyperfibrosis is mediated by TGF-β signaling pathway. J. Ovarian Res., 2018, 11(1), 6.
[http://dx.doi.org/10.1186/s13048-017-0375-7] [PMID: 29321035]
[33]
Teng, L.; Peng, S.; Guo, H.; Liang, H.; Xu, Z.; Su, Y.; Gao, L. Conditioned media from human ovarian cancer endothelial progenitor cells induces ovarian cancer cell migration by activating epithelial-to-mesenchymal transition. Cancer Gene Ther., 2015, 22(11), 518-523.
[http://dx.doi.org/10.1038/cgt.2015.45] [PMID: 26494557]
[34]
Dean, M.; Davis, D.A.; Burdette, J.E. Activin A stimulates migration of the fallopian tube epithelium, an origin of high-grade serous ovarian cancer, through non-canonical signaling. Cancer Lett., 2017, 391, 114-124.
[http://dx.doi.org/10.1016/j.canlet.2017.01.011] [PMID: 28115208]
[35]
Laping, N.J.; Everitt, J.I.; Frazier, K.S.; Burgert, M.; Portis, M.J.; Cadacio, C.; Gold, L.I.; Walker, C.L. Tumor-specific efficacy of transforming growth factor-β RI inhibition in eker rats. Clin. Cancer Res., 2007, 13(10), 3087-3099.
[http://dx.doi.org/10.1158/1078-0432.CCR-06-1811] [PMID: 17505012]
[36]
Hover, L.D.; Young, C.D.; Bhola, N.E.; Wilson, A.J.; Khabele, D.; Hong, C.C.; Moses, H.L.; Owens, P. Small molecule inhibitor of the bone morphogenetic protein pathway DMH1 reduces ovarian cancer cell growth. Cancer Lett., 2015, 368(1), 79-87.
[http://dx.doi.org/10.1016/j.canlet.2015.07.032] [PMID: 26235139]
[37]
Alsina-Sanchis, E.; Figueras, A.; Lahiguera, Á.; Vidal, A.; Casanovas, O.; Graupera, M.; Villanueva, A.; Viñals, F. The TGF-β pathway stimulates ovarian cancer cell proliferation by increasing IGF1R levels. Int. J. Cancer, 2016, 139(8), 1894-1903.
[http://dx.doi.org/10.1002/ijc.30233] [PMID: 27299695]
[38]
Gao, Y.; Shan, N.; Zhao, C.; Wang, Y.; Xu, F.; Li, J.; Yu, X.; Gao, L.; Yi, Z. LY2109761 enhances cisplatin antitumor activity in ovarian cancer cells. Int. J. Clin. Exp. Pathol., 2015, 8(5), 4923-4932.
[PMID: 26191185]
[39]
Hempel, N.; How, T.; Dong, M.; Murphy, S.K.; Fields, T.A.; Blobe, G.C. Loss of betaglycan expression in ovarian cancer: role in motility and invasion. Cancer Res., 2007, 67(11), 5231-5238.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-0035] [PMID: 17522389]
[40]
Florio, P.; Ciarmela, P.; Reis, F.M.; Toti, P.; Galleri, L.; Santopietro, R.; Tiso, E.; Tosi, P.; Petraglia, F. Inhibin α-subunit and the inhibin coreceptor betaglycan are downregulated in endometrial carcinoma. Eur. J. Endocrinol., 2005, 152(2), 277-284.
[http://dx.doi.org/10.1530/eje.1.01849] [PMID: 15745937]
[41]
Zakrzewski, P.K.; Mokrosinski, J.; Cygankiewicz, A.I.; Semczuk, A.; Rechberger, T.; Skomra, D.; Krajewska, W.M. Dysregulation of betaglycan expression in primary human endometrial carcinomas. Cancer Invest., 2011, 29(2), 137-144.
[http://dx.doi.org/10.3109/07357907.2010.543213] [PMID: 21261473]
[42]
Zakrzewski, P.K.; Nowacka-Zawisza, M.; Semczuk, A.; Rechberger, T.; Gałczyński, K.; Krajewska, W.M. Significance of TGFBR3 allelic loss in the deregulation of TGF-β signaling in primary human endometrial carcinomas. Oncol. Rep., 2016, 35(2), 932-938.
[http://dx.doi.org/10.3892/or.2015.4400] [PMID: 26548418]
[43]
De Gramont, A.; Faivre, S.; Raymond, E. Novel TGF-β inhibitors ready for prime time in onco-immunology. OncoImmunology, 2016, 6(1), e1257453.
[http://dx.doi.org/10.1080/2162402X.2016.1257453] [PMID: 28197376]
[44]
Makker, V.; Filiaci, V.L.; Chen, L.M.; Darus, C.J.; Kendrick, J.E.; Sutton, G.; Moxley, K.; Aghajanian, C. Phase II evaluation of dalantercept, a soluble recombinant Activin receptor-Like Kinase 1 (ALK1) receptor fusion protein, for the treatment of recurrent or persistent endometrial cancer: an NRG oncology/gynecologic oncology group study 0229N. Gynecol. Oncol., 2015, 138(1), 24-29.
[http://dx.doi.org/10.1016/j.ygyno.2015.04.006] [PMID: 25888978]
[45]
Burger, R. A.; Deng, W.; Makker, V.; Lankes, H.A.; Aghajanian, C.; Gray, H. J.; Wade, J. L.; Waggoner, S. E.; Levine, D. A. PHASE II evaluation of dalantercept for persistent or recurrent epithelial ovarian and related cancers: An NRG oncology study. J. Clin. Oncol., 2016, 34(15)(_suppl), e17050-e17050.
[46]
Oh, J.; Barve, M.; Matthews, C.M.; Koon, E.C.; Heffernan, T.P.; Fine, B.; Grosen, E.; Bergman, M.K.; Fleming, E.L.; DeMars, L.R.; West, L.; Spitz, D.L.; Goodman, H.; Hancock, K.C.; Wallraven, G.; Kumar, P.; Bognar, E.; Manning, L.; Pappen, B.O.; Adams, N.; Senzer, N.; Nemunaitis, J. Phase II study of vigil® DNA engineered immunotherapy as maintenance in advanced stage ovarian cancer. Gynecol. Oncol., 2016, 143(3), 504-510.
[http://dx.doi.org/10.1016/j.ygyno.2016.09.018] [PMID: 27678295]
[47]
ClinicalTrials.gov. 2011. Available from: https://clinicaltrials.gov/ct2/show/NCT01309230?term=NCT01309230&rank=1 (Assessedon June 10th, 2022)
[48]
Senzer, N.; Barve, M.; Kuhn, J.; Melnyk, A.; Beitsch, P.; Lazar, M.; Lifshitz, S.; Magee, M.; Oh, J.; Mill, S.W.; Bedell, C.; Higgs, C.; Kumar, P.; Yu, Y.; Norvell, F.; Phalon, C.; Taquet, N.; Rao, D.D.; Wang, Z.; Jay, C.M.; Pappen, B.O.; Wallraven, G.; Brunicardi, F.C.; Shanahan, D.M.; Maples, P.B.; Nemunaitis, J. Phase I trial of “bi-shRNAi(furin)/GMCSF DNA/autologous tumor cell” vaccine (FANG) in advanced cancer. Mol. Ther., 2012, 20(3), 679-686.
[http://dx.doi.org/10.1038/mt.2011.269] [PMID: 22186789]
[49]
Senzer, N.; Barve, M.; Nemunaitis, J.; Kuhn, J.; Melnyk, A.; Beitsch, P. Long term follow up: phase I trial of “bi-shRNA furin/GMCSF DNA/autologous tumor cell” immunotherapy (FANG™) in advanced cancer. J. Vaccines Vaccin., 2013, 4(8), 209.
[50]
ClinicalTrials.gov. 2019. Available from: https://clinicaltrials.gov/ct2/show/NCT03842865?term=NCT03842865&rank=1 (Assessed on June 10th,2022)
[51]
Oh, J.; Barve, M.A.; Tewari, D.; Chan, J.K.; Grosen, E.; Rocconi, R.P.; Stevens, E.E.; DeMars, L.R.; Ghamande, S. A.; Coleman, R.L.; Manning, L.; Wallraven, G.; Senzer, N.N.; Birkhofer, M.; Nemunaitis, J.J. Clinical trial in progress: A phase 3 study of maintenance bi-shRNA-furin/GM-CSF-expressing autologous tumor cell vaccine in women with stage IIIb-IV high-grade epithelial ovarian cancer. J. Clin. Oncol., 2017, 35(15)(_suppl.), TPS5604-TPS5604.
[52]
ClinicalTrials.gov. 2016. Available from: https://clinicaltrials.gov/ct2/show/NCT02725489?term=NCT02725489&rank=1 (Assessed on June 10th,2022)
[53]
ClinicalTrials.gov. 2017. Available from: https://clinicaltrials.gov/ct2/show/NCT03073525?term=vigil&cond=cancer&draw=1 (Assessed on June 10th,2022)
[54]
ClinicalTrials.gov. 2012. Available from: https://clinicaltrials.gov/ct2/show/NCT01551745?term=NCT01551745&rank=1 (Assessed on June 10th,2022)
[55]
Nemunaitis, J.J.; Senzer, N.N.; Barve, M.A.; Oh, J.; Kumar, P.; Rao, D. Survival effect of bi-shRNAfurin/GMCSF DNA-based immunotherapy (FANG) in 123 advanced cancer patients to α-interferon-ELISPTOT response. J. Clin. Oncol., 2014, 32(15)(_suppl.), 3077-3077.
[http://dx.doi.org/10.1200/jco.2014.32.15_suppl.3077]
[56]
ClinicalTrials.gov. 2013. Available from: https://clinicaltrials.gov/ct2/show/NCT01867086?term=NCT01867086&rank=1 (Assessed on June 10th,2022)
[57]
Crispim-Freitas, J.C.; Morais, R.S.; Oliveira, V.S.; Sadissou, I.; Palomino, G.M.; Cobucci, R.N. Influence of immune-checkpoint inhibitor and HLA-G in patients with Cervical Cancer. Am. Assoc. Immnol., 2019, 202(1)(Supplement), 136-210.
[58]
Oliva, M.; Spreafico, A.; Taberna, M.; Alemany, L.; Coburn, B.; Mesia, R.; Siu, L.L. Immune biomarkers of response to immune-checkpoint inhibitors in head and neck squamous cell carcinoma. Ann. Oncol., 2019, 30(1), 57-67.
[http://dx.doi.org/10.1093/annonc/mdy507] [PMID: 30462163]
[59]
Philips, G.K.; Atkins, M. Therapeutic uses of anti-PD-1 and anti-PD-L1 antibodies. Int. Immunol., 2015, 27(1), 39-46.
[http://dx.doi.org/10.1093/intimm/dxu095] [PMID: 25323844]
[60]
Sharma, P.; Allison, J.P. The future of immune checkpoint therapy. Science, 2015, 348(6230), 56-61.
[http://dx.doi.org/10.1126/science.aaa8172] [PMID: 25838373]
[61]
Orbegoso, C.; Murali, K.; Banerjee, S. The current status of immunotherapy for cervical cancer. Rep. Pract. Oncol. Radiother., 2018, 23(6), 580-588.
[http://dx.doi.org/10.1016/j.rpor.2018.05.001] [PMID: 30534022]
[62]
Kogo, R.; How, C.; Chaudary, N.; Bruce, J.; Shi, W.; Hill, R.P.; Zahedi, P.; Yip, K.W.; Liu, F.F. The microRNA-218~Survivin axis regulates migration, invasion, and lymph node metastasis in cervical cancer. Oncotarget, 2015, 6(2), 1090-1100.
[http://dx.doi.org/10.18632/oncotarget.2836] [PMID: 25473903]
[63]
Dong, W.; Li, B.; Wang, J.; Song, Y.; Zhang, Z.; Fu, C. MicroRNA-337 inhibits cell proliferation and invasion of cervical cancer through directly targeting specificity protein 1. Tumour Biol., 2017, 39(6), 1010428317711323.
[http://dx.doi.org/10.1177/1010428317711323] [PMID: 28641487]
[64]
Ma, D.; Zhang, Y-Y.; Guo, Y-L.; Li, Z-J.; Geng, L. Profiling of microRNA-mRNA reveals roles of microRNAs in cervical cancer. Chin. Med. J. (Engl.), 2012, 125(23), 4270-4276.
[PMID: 23217399]
[65]
Cheng, Y.; Guo, Y.; Zhang, Y.; You, K.; Li, Z.; Geng, L. MicroRNA-106b is involved in transforming growth factor β1-induced cell migration by targeting disabled homolog 2 in cervical carcinoma. J. Exp. Clin. Cancer Res., 2016, 35(1), 11.
[http://dx.doi.org/10.1186/s13046-016-0290-6] [PMID: 26769181]
[66]
Cao, L.; Jin, H.; Zheng, Y.; Mao, Y.; Fu, Z.; Li, X.; Dong, L. DANCR-mediated microRNA-665 regulates proliferation and metastasis of cervical cancer through the ERK/SMAD pathway. Cancer Sci., 2019, 110(3), 913-925.
[http://dx.doi.org/10.1111/cas.13921] [PMID: 30582654]
[67]
Chen, Z.; Pang, N.; Du, R.; Zhu, Y.; Fan, L.; Cai, D. Elevated expression of programmed death-1 and programmed death ligand-1 negatively regulates immune response against cervical cancer cells. Mediators Inflamm., 2016.
[http://dx.doi.org/10.1155/2016/6891482]
[68]
Dickson, J.; Davidson, S.E.; Hunter, R.D.; West, C.M. Pretreatment plasma TGFβ1 levels are prognostic for survival but not morbidity following radiation therapy of carcinoma of the cervix. Int. J. of Radiat. Oncol. Biol. Physics, 2000, 48(4), 991-995.
[http://dx.doi.org/10.1016/S0360-3016(00)00729-X]
[69]
Fan, D.M.; Wang, X.J.; He, T.; Wang, Y.; Zhou, D.; Kong, G.Q.; Jiang, T.; Zhang, M.M. High expression of TGF-β1 in the vaginal incisional margin predicts poor prognosis in patients with stage Ib-IIa cervical squamous cell carcinoma. Mol. Biol. Rep., 2012, 39(4), 3925-3931.
[http://dx.doi.org/10.1007/s11033-011-1171-x] [PMID: 21773949]
[70]
Baritaki, S.; Sifakis, S.; Huerta-Yepez, S.; Neonakis, I.K.; Soufla, G.; Bonavida, B.; Spandidos, D.A. Overexpression of VEGF and TGF-β1 mRNA in Pap smears correlates with progression of cervical intraepithelial neoplasia to cancer: implication of YY1 in cervical tumorigenesis and HPV infection. Int. J. Oncol., 2007, 31(1), 69-79.
[http://dx.doi.org/10.3892/ijo.31.1.69] [PMID: 17549406]
[71]
Haapasalmi, K.; Zhang, K.; Tonnesen, M.; Olerud, J.; Sheppard, D.; Salo, T.; Kramer, R.; Clark, R.A.; Uitto, V.J.; Larjava, H. Keratinocytes in human wounds express α v β 6 integrin. J. Invest. Dermatol., 1996, 106(1), 42-48.
[http://dx.doi.org/10.1111/1523-1747.ep12327199] [PMID: 8592080]
[72]
Hazelbag, S; Kenter, GG; Gorter, A; Dreef, EJ; Koopman, LA; Violette, SM Overexpression of the αvβ6 integrin in cervical squamous cell carcinoma is a prognostic factor for decreased survival. J. Pathol., 2007, 212(3), 316-24.
[http://dx.doi.org/10.1002/path.2168]
[73]
Li, D.Y.; Sorensen, L.K.; Brooke, B.S.; Urness, L.D.; Davis, E.C.; Taylor, D.G.; Boak, B.B.; Wendel, D.P. Defective angiogenesis in mice lacking endoglin. Science, 1999, 284(5419), 1534-1537.
[http://dx.doi.org/10.1126/science.284.5419.1534] [PMID: 10348742]
[74]
Nassiri, F.; Cusimano, M.D.; Scheithauer, B.W.; Rotondo, F.; Fazio, A.; Yousef, G.M.; Syro, L.V.; Kovacs, K.; Lloyd, R.V. Endoglin (CD105): a review of its role in angiogenesis and tumor diagnosis, progression and therapy. Anticancer Res., 2011, 31(6), 2283-2290.
[PMID: 21737653]
[75]
Lin, H.; Huang, C-C.; Ou, Y-C.; Huang, E-Y.; Changchien, C.C.; Tseng, C.W.; Fu, H.C.; Wu, C.H.; Li, C.J.; Ma, Y.Y. High immunohisto-chemical expression of TGF-β1 predicts a poor prognosis in cervical cancer patients who harbor enriched endoglin microvessel density. Int. J. Gynecol. Pathol., 2012, 31(5), 482-489.
[http://dx.doi.org/10.1097/PGP.0b013e31824c23a4] [PMID: 22833091]
[76]
Dai, W.; Zhong, L.; He, J.; Zhao, Y. Targeting endoglin for cancer diagnosis and therapy: current state and future promise. Discov. Med., 2019, 28(152), 87-93.
[PMID: 31926580]
[77]
Barriuso, B.; Antolín, P.; Arias, F.J.; Girotti, A.; Jiménez, P.; Cordoba-Diaz, M.; Cordoba-Diaz, D.; Girbés, T. Anti-human endoglin (hCD105) immunotoxin-containing recombinant single chain ribosome-inactivating protein musarmin 1. Toxins (Basel), 2016, 8(6), 184.
[http://dx.doi.org/10.3390/toxins8060184] [PMID: 27294959]
[78]
Opławski, M.; Dziobek, K.; Adwent, I.; Dąbruś, D.; Grabarek, B.; Zmarzły, N.; Plewka, A.; Boroń, D. Expression profile of endoglin in different grades of endometrial cancer. Curr. Pharm. Biotechnol., 2018, 19(12), 990-995.
[http://dx.doi.org/10.2174/1389201020666181127152605] [PMID: 30479213]
[79]
Fan, D-M.; Tian, X-Y.; Wang, R-F.; Yu, J-J. The prognosis significance of TGF-β1 and ER protein in cervical adenocarcinoma patients with stage Ib~IIa. Tumour Biol., 2014, 35(11), 11237-11242.
[http://dx.doi.org/10.1007/s13277-014-2110-y] [PMID: 25113249]
[80]
Yang, H.; Zhang, H.; Zhong, Y.; Wang, Q.; Yang, L.; Kang, H.; Gao, X.; Yu, H.; Xie, C.; Zhou, F.; Zhou, Y. Concomitant underexpression of TGFBR2 and overexpression of hTERT are associated with poor prognosis in cervical cancer. Sci. Rep., 2017, 7(1), 41670.
[http://dx.doi.org/10.1038/srep41670] [PMID: 28195144]
[81]
Wang, D.G.; Li, T.M.; Liu, X. RHCG suppresses cervical cancer progression through inhibiting migration and inducing apoptosis regulated by TGF-β1. Biochem. Biophys. Res. Commun., 2018, 503(1), 86-93.
[http://dx.doi.org/10.1016/j.bbrc.2018.05.183] [PMID: 29852177]
[82]
Hale, J.S.; Otvos, B.; Sinyuk, M.; Alvarado, A.G.; Hitomi, M.; Stoltz, K.; Wu, Q.; Flavahan, W.; Levison, B.; Johansen, M.L.; Schmitt, D.; Neltner, J.M.; Huang, P.; Ren, B.; Sloan, A.E.; Silverstein, R.L.; Gladson, C.L.; DiDonato, J.A.; Brown, J.M.; McIntyre, T.; Hazen, S.L.; Horbinski, C.; Rich, J.N.; Lathia, J.D. Cancer stem cell-specific scavenger receptor CD36 drives glioblastoma progression. Stem Cells, 2014, 32(7), 1746-1758.
[http://dx.doi.org/10.1002/stem.1716] [PMID: 24737733]
[83]
Deng, M.; Cai, X.; Long, L.; Xie, L.; Ma, H.; Zhou, Y.; Liu, S.; Zeng, C. CD36 promotes the epithelial-mesenchymal transition and metastasis in cervical cancer by interacting with TGF-β. J. Transl. Med., 2019, 17(1), 352.
[http://dx.doi.org/10.1186/s12967-019-2098-6] [PMID: 31655604]
[84]
Pascual, G.; Avgustinova, A.; Mejetta, S.; Martín, M.; Castellanos, A.; Attolini, C.S-O.; Berenguer, A.; Prats, N.; Toll, A.; Hueto, J.A.; Bescós, C.; Di Croce, L.; Benitah, S.A. Targeting metastasis-initiating cells through the fatty acid receptor CD36. Nature, 2017, 541(7635), 41-45.
[http://dx.doi.org/10.1038/nature20791] [PMID: 27974793]
[85]
Mansoori, M.; Roudi, R.; Abbasi, A.; Abolhasani, M.; Abdi Rad, I.; Shariftabrizi, A.; Madjd, Z. High GD2 expression defines breast cancer cells with enhanced invasiveness. Exp. Mol. Pathol., 2019, 109, 25-35.
[http://dx.doi.org/10.1016/j.yexmp.2019.05.001] [PMID: 31075227]
[86]
ClinicalTrials.gov. 2016. Available from: https://clinicaltrials.gov/ct2/show/NCT02725489?term=NCT02725489&rank=1 (Assessed on June 10th,2022)

Rights & Permissions Print Cite
Article Metrics
30
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy