CAP1 is overexpressed in human epithelial ovarian cancer and promotes cell proliferation

Hua,Minhui; Yan,Sujuan; Deng,Yan; Xi,Qinghua; Liu,Rong; Yang,Shuyun; Liu,Jian; Tang,Chunhui; Wang,Yingying; Zhong,Jianxin

doi:10.3892/ijmm.2015.2089

CAP1 is overexpressed in human epithelial ovarian cancer and promotes cell proliferation

Authors:
- Minhui Hua
- Sujuan Yan
- Yan Deng
- Qinghua Xi
- Rong Liu
- Shuyun Yang
- Jian Liu
- Chunhui Tang
- Yingying Wang
- Jianxin Zhong
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Affiliations: Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Oncology, Nantong University Cancer Hospital, Nantong, Jiangsu 226001, P.R. China, Department of Pathology, Nantong University Cancer Hospital, Nantong, Jiangsu 226001, P.R. China, Department of Pathogen Biology, Medical College, Nantong University, Nantong, Jiangsu 226001, P.R. China
Published online on: February 4, 2015 https://doi.org/10.3892/ijmm.2015.2089
Pages: 941-949
Copyright: © Hua et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Adenylate cyclase-associated protein 1 (CAP1) regulates both actin filaments and the Ras/cAMP pathway in yeast, and has been found play a role in cell motility and in the development of certain types of cancer. In the present study, we investigated CAP1 gene expression in human epithelial ovarian cancer (EOC). Western blot analysis and immunohistochemistry were performed using EOC tissue samples and the results revealed that CAP1 expression increased with the increasing grade of EOC. In the normal ovarian tissue samples however, CAP1 expression was barely detected. Using Pearson's χ2 test, it was demonstrated that CAP1 expression was associated with the histological grade and Ki-67 expression. Kaplan-Meier analysis revealed that a higher CAP1 expression in patients with EOC was associated with a poorer prognosis. In in vitro experiments using HO-8910 EOC cells, the expression of CAP1 was knocked down using siRNA. The proliferation of the HO-8910 cells was then determined by cell cycle analysis and cell proliferation assay using the cell counting kit-8 and flow cytometry. The results revealed that the loss of CAP1 expression inhibited cell cycle progression. These findings suggest that a high expression of CAP1 is involved in the pathogenesis of EOC, and that the downregulation of CAP1 in tumor cells may be a therapeutic target for the treatment of patients with EOC.

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1	Menczer J, Chetrit A and Sadetzki S; National Israel Ovarian Cancer Group: Uterine metastases in ovarian carcinoma: frequency and survival in women who underwent hysterectomy. J Gynecol Oncol. 21:191–195. 2010. View Article : Google Scholar : PubMed/NCBI
2	Park B, Park S, Kim TJ, et al: Epidemiological characteristics of ovarian cancer in Korea. J Gynecol Oncol. 21:241–247. 2010. View Article : Google Scholar
3	Chang E, Heo KS, Woo CH, et al: MK2 SUMOylation regulates actin filament remodeling and subsequent migration in endothelial cells by inhibiting MK2 kinase and HSP27 phosphorylation. Blood. 117:2527–2537. 2011. View Article : Google Scholar :
4	Kirfel G, Rigort A, Borm B and Herzog V: Cell migration: mechanisms of rear detachment and the formation of migration tracks. Eur J Cell Biol. 83:717–724. 2004. View Article : Google Scholar
5	Hall A: The cytoskeleton and cancer. Cancer Metastasis Rev. 28:5–14. 2009. View Article : Google Scholar : PubMed/NCBI
6	Makkonen M, Bertling E, Chebotareva NA, Baum J and Lappalainen P: Mammalian and malaria parasite cyclase-associated proteins catalyze nucleotide exchange on G-actin through a conserved mechanism. J Biol Chem. 288:984–994. 2013. View Article : Google Scholar :
7	Fedor-Chaiken M, Deschenes RJ and Broach JR: SRV2, a gene required for RAS activation of adenylate cyclase in yeast. Cell. 61:329–340. 1990. View Article : Google Scholar : PubMed/NCBI
8	Field J, Vojtek A, Ballester R, et al: Cloning and characterization of CAP, the S. cerevisiae gene encoding the 70 kd adenylyl cyclase-associated protein. Cell. 61:319–327. 1990. View Article : Google Scholar : PubMed/NCBI
9	Peche V, Shekar S, Leichter M, et al: CAP2, cyclase-associated protein 2, is a dual compartment protein. Cell Mol Life Sci. 64:2702–2715. 2007. View Article : Google Scholar : PubMed/NCBI
10	Matviw H, Yu G and Young D: Identification of a human cDNA encoding a protein that is structurally and functionally related to the yeast adenylyl cyclase-associated CAP proteins. Mol Cell Biol. 12:5033–5040. 1992.PubMed/NCBI
11	Zelicof A, Gatica J and Gerst JE: Molecular cloning and characterization of a rat homolog of CAP, the adenylyl cyclase-associated protein from Saccharomyces cerevisiae. J Biol Chem. 268:13448–13453. 1993.PubMed/NCBI
12	Yu G, Swiston J and Young D: Comparison of human CAP and CAP2, homologs of the yeast adenylyl cyclase-associated proteins. J Cell Sci. 107:1671–1678. 1994.PubMed/NCBI
13	Swiston J, Hubberstey A, Yu G and Young D: Differential expression of CAP and CAP2 in adult rat tissues. Gene. 165:273–277. 1995. View Article : Google Scholar : PubMed/NCBI
14	Pollard TD and Cooper JA: Actin, a central player in cell shape and movement. Science. 326:1208–1212. 2009. View Article : Google Scholar : PubMed/NCBI
15	Baum B, Li W and Perrimon N: A cyclase-associated protein regulates actin and cell polarity during Drosophila oogenesis and in yeast. Curr Biol. 10:964–973. 2000. View Article : Google Scholar : PubMed/NCBI
16	Baum B and Perrimon N: Spatial control of the actin cytoskeleton in Drosophila epithelial cells. Nat Cell Biol. 3:883–890. 2001. View Article : Google Scholar : PubMed/NCBI
17	Hubberstey AV and Mottillo EP: Cyclase-associated proteins: CAPacity for linking signal transduction and actin polymerization. FASEB J. 16:487–499. 2002. View Article : Google Scholar : PubMed/NCBI
18	Kang CM and Jiang YW: Genome-wide survey of non-essential genes required for slowed DNA synthesis-induced filamentous growth in yeast. Yeast. 22:79–90. 2005. View Article : Google Scholar : PubMed/NCBI
19	Yusof AM, Hu NJ, Wlodawer A and Hofmann A: Structural evidence for variable oligomerization of the N-terminal domain of cyclase-associated protein (CAP). Proteins. 58:255–262. 2005. View Article : Google Scholar
20	Loisel TP, Boujemaa R, Pantaloni D and Carlier MF: Reconstitution of actin-based motility of Listeria and Shigella using pure proteins. Nature. 401:613–616. 1999. View Article : Google Scholar : PubMed/NCBI
21	Pollard TD, Blanchoin L and Mullins RD: Molecular mechanisms controlling actin filament dynamics in nonmuscle cells. Annu Rev Biophys Biomol Struct. 29:545–576. 2000. View Article : Google Scholar : PubMed/NCBI
22	Bertling E, Hotulainen P, Mattila PK, Matilainen T, Salminen M and Lappalainen P: Cyclase-associated protein 1 (CAP1) promotes cofilin-induced actin dynamics in mammalian nonmuscle cells. Mol Biol Cell. 15:2324–2334. 2004. View Article : Google Scholar : PubMed/NCBI
23	Wang C, Zhou GL, Vedantam S, Li P and Field J: Mitochondrial shuttling of CAP1 promotes actin- and cofilin-dependent apoptosis. J Cell Sci. 121:2913–2920. 2008. View Article : Google Scholar : PubMed/NCBI
24	Liu Y, Cui X, Hu B, et al: Upregulated expression of CAP1 is associated with tumor migration and metastasis in hepatocellular carcinoma. Pathol Res Pract. 210:169–175. 2014. View Article : Google Scholar
25	Yu XF, Ni QC, Chen JP, et al: Knocking down the expression of adenylate cyclase-associated protein 1 inhibits the proliferation and migration of breast cancer cells. Exp Mol Pathol. 96:188–194. 2014. View Article : Google Scholar : PubMed/NCBI
26	Tan M, Song X, Zhang G, et al: Overexpression of adenylate cyclase-associated protein 1 is associated with metastasis of lung cancer. Oncol Rep. 30:1639–1644. 2013.PubMed/NCBI
27	Li M, Yang X, Shi H, et al: Downregulated expression of the cyclase-associated protein 1 (CAP1) reduces migration in esophageal squamous cell carcinoma. Jpn J Clin Oncol. 43:856–864. 2013. View Article : Google Scholar : PubMed/NCBI
28	Zelicof A, Protopopov V, David D, Lin XY, Lustgarten V and Gerst JE: Two separate functions are encoded by the carboxyl-terminal domains of the yeast cyclase-associated protein and its mammalian homologs. Dimerization and actin binding. J Biol Chem. 271:18243–18252. 1996. View Article : Google Scholar : PubMed/NCBI
29	Noegel AA, Blau-Wasser R, Sultana H, et al: The cyclase-associated protein CAP as regulator of cell polarity and cAMP signaling in Dictyostelium. Mol Biol Cell. 15:934–945. 2004. View Article : Google Scholar :
30	Gerst JE, Ferguson K, Vojtek A, Wigler M and Field J: CAP is a bifunctional component of the Saccharomyces cerevisiae adenylyl cyclase complex. Mol Cell Biol. 11:1248–1257. 1991.PubMed/NCBI
31	Vojtek A, Haarer B, Field J, et al: Evidence for a functional link between profilin and CAP in the yeast S cerevisiae. Cell. 66:497–505. 1991. View Article : Google Scholar : PubMed/NCBI
32	Yamazaki K, Takamura M, Masugi Y, et al: Adenylate cyclase-associated protein 1 overexpressed in pancreatic cancers is involved in cancer cell motility. Lab Invest. 89:425–432. 2009. View Article : Google Scholar : PubMed/NCBI
33	Friedl P and Wolf K: Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer. 3:362–374. 2003. View Article : Google Scholar : PubMed/NCBI
34	Moriyama K and Yahara I: Human CAP1 is a key factor in the recycling of cofilin and actin for rapid actin turnover. J Cell Sci. 115:1591–1601. 2002.PubMed/NCBI