ATP‑binding cassette transporter A7 accelerates epithelial‑to‑mesenchymal transition in ovarian cancer cells by upregulating the transforming growth factor‑β signaling pathway

Liu,Xia; Li,Qing; Zhou,Jing; Zhang,Su

doi:10.3892/ol.2018.9366

ATP‑binding cassette transporter A7 accelerates epithelial‑to‑mesenchymal transition in ovarian cancer cells by upregulating the transforming growth factor‑β signaling pathway

Authors:
- Xia Liu
- Qing Li
- Jing Zhou
- Su Zhang
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Affiliations: Department of Gynecology and Obstetrics, Jining No. 1 People's Hospital, Jining, Shandong 272111, P.R. China, Department of Nursing, Jining No. 1 People's Hospital, Jining, Shandong 272111, P.R. China
Published online on: August 24, 2018 https://doi.org/10.3892/ol.2018.9366
Pages: 5868-5874
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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1	Nezhat FR, Apostol R, Nezhat C and Pejovic T: New insights in the pathophysiology of ovarian cancer and implications for screening and prevention. Am J Obstet Gynecol. 213:262–267. 2015. View Article : Google Scholar : PubMed/NCBI
2	Yeung TL, Leung CS, Yip KP, Au Yeung CL, Wong ST and Mok SC: 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. 309:C444–C456. 2015. View Article : Google Scholar : PubMed/NCBI
3	Tan TZ, Miow QH, Miki Y, Noda T, Mori S, Huang RY and Thiery JP: Epithelial-mesenchymal transition spectrum quantification and its efficacy in deciphering survival and drug responses of cancer patients. EMBO Mol Med. 6:1279–1293. 2014. View Article : Google Scholar : PubMed/NCBI
4	Elsnerova K, Mohelnikova-Duchonova B, Cerovska E, Ehrlichova M, Gut I, Rob L, Skapa P, Hruda M, Bartakova A, Bouda J, et al: Gene expression of membrane transporters: Importance for prognosis and progression of ovarian carcinoma. Oncol Rep. 35:2159–2170. 2016. View Article : Google Scholar : PubMed/NCBI
5	Elsnerova K, Bartakova A, Tihlarik J, Bouda J, Rob L, Skapa P, Hruda M, Gut I, Mohelnikova-Duchonova B, Soucek P and Vaclavikova R: Gene expression profiling reveals novel candidate markers of ovarian carcinoma intraperitoneal metastasis. J Cancer. 8:3598–3606. 2017. View Article : Google Scholar : PubMed/NCBI
6	Hedditch EL, Gao B, Russell AJ, Lu Y, Emmanuel C, Beesley J, Johnatty SE, Chen X, Harnett P, George J, et al: ABCA transporter gene expression and poor outcome in epithelial ovarian cancer. J Natl Cancer Inst. 106:dju1492014. View Article : Google Scholar : PubMed/NCBI
7	Hlavata I, Mohelnikova-Duchonova B, Vaclavikova R, Liska V, Pitule P, Novak P, Bruha J, Vycital O, Holubec L, Treska V, et al: The role of ABC transporters in progression and clinical outcome of colorectal cancer. Mutagenesis. 27:187–196. 2012. View Article : Google Scholar : PubMed/NCBI
8	Li W, Zhang X, Wang J, Li M, Cao C, Tan J, Ma D and Gao Q: TGFβ1 in fibroblasts-derived exosomes promotes epithelial-mesenchymal transition of ovarian cancer cells. Oncotarget. 8:96035–96047. 2017.PubMed/NCBI
9	Yeung TL, Leung CS, Wong KK, Samimi G, Thompson MS, Liu J, Zaid TM, Ghosh S, Birrer MJ and Mok SC: TGF-β modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment. Cancer Res. 73:5016–5028. 2013. View Article : Google Scholar : PubMed/NCBI
10	Luo L, McGarvey P, Madhavan S, Kumar R, Gusev Y and Upadhyay G: Distinct lymphocyte antigens 6 (Ly6) family members Ly6D, Ly6E, Ly6K and Ly6H drive tumorigenesis and clinical outcome. Oncotarget. 7:11165–11193. 2016. View Article : Google Scholar : PubMed/NCBI
11	Goswami CP and Nakshatri H: PROGgeneV2: Enhancements on the existing database. BMC Cancer. 14:9702014. View Article : Google Scholar : PubMed/NCBI
12	Dong P, Xiong Y, Watari H, Hanley Sharon JB, Konno Y, Ihira K, Yamada T, Kudo M, Yue J and Sakuragi N: MiR-137 and miR-34a directly target Snail and inhibit EMT, invasion and sphere-forming ability of ovarian cancer cells. J Exp Clin Canc Res. 35:1322016. View Article : Google Scholar
13	Yan F, Wang X, Shao L, Ge M and Hu X: Analysis of UHRF1 expression in human ovarian cancer tissues and its regulation in cancer cell growth. Tumour Biol. 36:8887–8893. 2015. View Article : Google Scholar : PubMed/NCBI
14	Tang X, Shi L, Xie N, Liu Z, Qian M, Meng F, Xu Q, Zhou M, Cao X, Zhu WG and Liu B: SIRT7 antagonizes TGF-β signaling and inhibits breast cancer metastasis. Nat Commun. 8:3182017. View Article : Google Scholar : PubMed/NCBI
15	Chen IC, Chiang WF, Huang HH, Chen PF, Shen YY and Chiang HC: Role of SIRT1 in regulation of epithelial-to-mesenchymal transition in oral squamous cell carcinoma metastasis. Mol Cancer. 13:2542014. View Article : Google Scholar : PubMed/NCBI
16	Sopik V, Rosen B, Giannakeas V and Narod SA: Why have ovarian cancer mortality rates declined? Part III. Prospects for the future. Gynecol Oncol. 138:757–761. 2015. View Article : Google Scholar : PubMed/NCBI
17	Savagner P: Epithelial-mesenchymal transitions: From cell plasticity to concept elasticity. Curr Top Dev Biol. 112:273–300. 2015. View Article : Google Scholar : PubMed/NCBI
18	Nakayama K, Nakayama N, Katagiri H and Miyazaki K: Mechanisms of ovarian cancer metastasis: Biochemical pathways. Int J Mol Sci. 13:11705–11717. 2012. View Article : Google Scholar : PubMed/NCBI
19	Shirakihara T, Saitoh M and Miyazono K: Differential regulation of epithelial and mesenchymal markers by δEF1 proteins in epithelial-mesenchymal transition induced by TGF-β. Mol Biol Cell. 18:3533–3544. 2007. View Article : Google Scholar : PubMed/NCBI