ATP-binding Cassette Transporter A7 Accelerates Epithelial-to-mesenchymal Transition in Ovarian Cancer Cells by Upregulating the Transforming Growth Factor-β Signaling Pathway

Overview

Journal Oncol Lett

Specialty Oncology

Date 2018 Oct 19

PMID 30333865

Citations 12

Authors

Xia Liu

Qing Li

Jing Zhou

Su Zhang

Affiliations

Soon will be listed here.

Abstract

Ovarian cancer (OC) has the highest fatality rates of all gynecological malignancies worldwide. The epithelial-to-mesenchymal transition (EMT) serves an essential role in the progression of OC. An improved understanding of the molecular mechanism underlying EMT in OC may increase the survival rate. ATP-binding cassette transporter A7 (ABCA7) is a candidate regulator of OC progression. However, the role of ABCA7 in OC is unclear. Using the PROGgeneV2 platform, the present study revealed that increased expression of ABCA7 is associated with poor outcomes in OC. The expression of ABCA7 was higher in OC tissues than in adjacent noncancerous tissues. ABCA7-knockdown decreased the migration of OC cells and the activation of mothers against decapentaplegic homolog 4 (SMAD4). Notably, downregulation of ABCA7 also increased the expression of an epithelial marker (E-cadherin) and decreased that of a mesenchymal marker (N-cadherin). In addition, the decreased expression of SMAD4 and EMT markers induced by ABCA7 depletion could be rescued by transforming growth factor β1 (TGF-β1) stimulation. Overall, these findings suggested that ABCA7 accelerates EMT in OC by upregulating the TGF-β signaling pathway.

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References

Savagner P . Epithelial-mesenchymal transitions: from cell plasticity to concept elasticity. Curr Top Dev Biol. 2015; 112:273-300. DOI: 10.1016/bs.ctdb.2014.11.021. View

Nezhat F, Apostol R, Nezhat C, Pejovic T . New insights in the pathophysiology of ovarian cancer and implications for screening and prevention. Am J Obstet Gynecol. 2015; 213(3):262-7. DOI: 10.1016/j.ajog.2015.03.044. View

Yeung T, Leung C, Yip K, Yeung C, Wong S, C Mok S . Cellular and molecular processes in ovarian cancer metastasis. A Review in the Theme: Cell and Molecular Processes in Cancer Metastasis. Am J Physiol Cell Physiol. 2015; 309(7):C444-56. PMC: 4593771. DOI: 10.1152/ajpcell.00188.2015. View

Yan F, Wang X, Shao L, Ge M, Hu X . Analysis of UHRF1 expression in human ovarian cancer tissues and its regulation in cancer cell growth. Tumour Biol. 2015; 36(11):8887-93. DOI: 10.1007/s13277-015-3638-1. View

Luo L, McGarvey P, Madhavan S, Kumar R, Gusev Y, Upadhyay G . Distinct lymphocyte antigens 6 (Ly6) family members Ly6D, Ly6E, Ly6K and Ly6H drive tumorigenesis and clinical outcome. Oncotarget. 2016; 7(10):11165-93. PMC: 4905465. DOI: 10.18632/oncotarget.7163. View

Tang X, Shi L, Xie N, Liu Z, Qian M, Meng F . SIRT7 antagonizes TGF-β signaling and inhibits breast cancer metastasis. Nat Commun. 2017; 8(1):318. PMC: 5566498. DOI: 10.1038/s41467-017-00396-9. View

Dong P, Xiong Y, Watari H, Hanley S, Konno Y, Ihira K . MiR-137 and miR-34a directly target Snail and inhibit EMT, invasion and sphere-forming ability of ovarian cancer cells. J Exp Clin Cancer Res. 2016; 35(1):132. PMC: 5011787. DOI: 10.1186/s13046-016-0415-y. View

Hedditch E, Gao B, Russell A, Lu Y, Emmanuel C, Beesley J . ABCA transporter gene expression and poor outcome in epithelial ovarian cancer. J Natl Cancer Inst. 2014; 106(7). PMC: 4110473. DOI: 10.1093/jnci/dju149. View

Li W, Zhang X, Wang J, Li M, Cao C, Tan J . TGFβ1 in fibroblasts-derived exosomes promotes epithelial-mesenchymal transition of ovarian cancer cells. Oncotarget. 2017; 8(56):96035-96047. PMC: 5707079. DOI: 10.18632/oncotarget.21635. View

10.

Shirakihara T, Saitoh M, Miyazono K . Differential regulation of epithelial and mesenchymal markers by deltaEF1 proteins in epithelial mesenchymal transition induced by TGF-beta. Mol Biol Cell. 2007; 18(9):3533-44. PMC: 1951739. DOI: 10.1091/mbc.e07-03-0249. View

11.

Sopik V, Rosen B, Giannakeas V, Narod S . Why have ovarian cancer mortality rates declined? Part III. Prospects for the future. Gynecol Oncol. 2015; 138(3):757-61. DOI: 10.1016/j.ygyno.2015.06.019. View

12.

Goswami C, Nakshatri H . PROGgeneV2: enhancements on the existing database. BMC Cancer. 2014; 14:970. PMC: 4300843. DOI: 10.1186/1471-2407-14-970. View

13.

Hlavata I, Mohelnikova-Duchonova B, Vaclavikova R, Liska V, Pitule P, Novak P . The role of ABC transporters in progression and clinical outcome of colorectal cancer. Mutagenesis. 2012; 27(2):187-96. DOI: 10.1093/mutage/ger075. View

14.

Tan T, Miow Q, Miki Y, Noda T, Mori S, Huang R . Epithelial-mesenchymal transition spectrum quantification and its efficacy in deciphering survival and drug responses of cancer patients. EMBO Mol Med. 2014; 6(10):1279-93. PMC: 4287932. DOI: 10.15252/emmm.201404208. View

15.

Elsnerova K, Bartakova A, Tihlarik J, Bouda J, Rob L, Skapa P . Gene Expression Profiling Reveals Novel Candidate Markers of Ovarian Carcinoma Intraperitoneal Metastasis. J Cancer. 2017; 8(17):3598-3606. PMC: 5687176. DOI: 10.7150/jca.20766. View

16.

Chen I, Chiang W, Huang H, Chen P, Shen Y, Chiang H . Role of SIRT1 in regulation of epithelial-to-mesenchymal transition in oral squamous cell carcinoma metastasis. Mol Cancer. 2014; 13:254. PMC: 4258025. DOI: 10.1186/1476-4598-13-254. View

17.

Yeung T, Leung C, Wong K, Samimi G, Thompson M, Liu J . TGF-β modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment. Cancer Res. 2013; 73(16):5016-28. PMC: 3745588. DOI: 10.1158/0008-5472.CAN-13-0023. View

18.

Nakayama K, Nakayama N, Katagiri H, Miyazaki K . Mechanisms of ovarian cancer metastasis: biochemical pathways. Int J Mol Sci. 2012; 13(9):11705-11717. PMC: 3472771. DOI: 10.3390/ijms130911705. View

19.

Elsnerova K, Mohelnikova-Duchonova B, Cerovska E, Ehrlichova M, Gut I, Rob L . Gene expression of membrane transporters: Importance for prognosis and progression of ovarian carcinoma. Oncol Rep. 2016; 35(4):2159-70. DOI: 10.3892/or.2016.4599. View