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Erschienen in: Medical Oncology 3/2014

01.03.2014 | Original Paper

High expression and prognostic role of CAP1 and CtBP2 in breast carcinoma: associated with E-cadherin and cell proliferation

verfasst von: Xiancheng Liu, Ninghua Yao, Jing Qian, Huiwei Huang

Erschienen in: Medical Oncology | Ausgabe 3/2014

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Abstract

Overexpression of C-terminal binding protein-2 (CtBP2) has been noted to correlate with cancer metastasis in several human cancers including breast cancer. The aim of this study was to examine the effect of cyclase-associated protein 1 (CAP1) overexpression on CtBP2 expression and related mechanism in the metastasis of breast cancer. Immunohistochemical analysis was performed in 100 human breast carcinoma samples, and the data were correlated with clinicopathologic features. Furthermore, Western blot analysis was performed for CAP1 and CtBP2 in breast carcinoma samples and cell lines to evaluate their protein levels and molecular interaction. We found that the expression of CAP1 was positively related to CtBP2 expression (P < 0.01); moreover, CAP1 expression was significantly correlated with histologic grade (P < 0.01) and negatively related to E-cadherin expression (P < 0.01). Meanwhile, CtBP2 expression obtained similar results. Kaplan–Meier survival analysis showed that overexpression of CAP1 and CtBP2 exhibited a significant correlation with poor prognosis in human breast cancer (P < 0.01). While in vitro, we employed siRNA technique to knockdown CAP1 and CtBP2 expressions and observed their effects on MDA-MB-231 cells growth. CtBP2 depletion by siRNA-inhibited cell proliferation, resulted in increased E-cadherin levels. Moreover, knockdown of CAP1 resulted in decreased CtBP2 and increased E-cadherin expression. On the basis of these results, we suggested that CAP1’s oncogenic abilities appear to be triggered at least in part by the modulation of CtBP2 and E-cadherin, which might serve as a future target for breast cancer.
Literatur
1.
Zurück zum Zitat Glass AG, Lacey JV Jr, Carreon JD, Hoover RN. Breast cancer incidence, 1980-2006: combined roles of menopausal hormone therapy, screening mammography, and estrogen receptor status. J Natl Cancer Inst. 2007;99:1152–61.PubMedCrossRef Glass AG, Lacey JV Jr, Carreon JD, Hoover RN. Breast cancer incidence, 1980-2006: combined roles of menopausal hormone therapy, screening mammography, and estrogen receptor status. J Natl Cancer Inst. 2007;99:1152–61.PubMedCrossRef
2.
Zurück zum Zitat Hubberstey AV, Mottillo EP. Cyclase-associated proteins: CAPacity for linking signal transduction and actin polymerization. FASEB J. 2002;16:487–99.PubMedCrossRef Hubberstey AV, Mottillo EP. Cyclase-associated proteins: CAPacity for linking signal transduction and actin polymerization. FASEB J. 2002;16:487–99.PubMedCrossRef
3.
Zurück zum Zitat Zhang H, Ghai P, Wu H, et al. Mammalian adenylyl cyclase-associated protein 1 (CAP1) regulates cofilin function, the actin cytoskeleton, and cell adhesion. J Biol Chem. 2013;288:20966–77.PubMedCrossRef Zhang H, Ghai P, Wu H, et al. Mammalian adenylyl cyclase-associated protein 1 (CAP1) regulates cofilin function, the actin cytoskeleton, and cell adhesion. J Biol Chem. 2013;288:20966–77.PubMedCrossRef
4.
Zurück zum Zitat Makkonen M, Bertling E, Chebotareva NA, et al. Mammalian and malaria parasite cyclase-associated proteins catalyze nucleotide exchange on G-actin through a conserved mechanism. J Biol Chem. 2013;288:984–94.PubMedCrossRef Makkonen M, Bertling E, Chebotareva NA, et al. Mammalian and malaria parasite cyclase-associated proteins catalyze nucleotide exchange on G-actin through a conserved mechanism. J Biol Chem. 2013;288:984–94.PubMedCrossRef
5.
Zurück zum Zitat Bertling E, Hotulainen P, Mattila PK, et al. Cyclase-associated protein 1 (CAP1) promotes cofilin-induced actin dynamics in mammalian nonmuscle cells. Mol Biol Cell. 2004;15:2324–34.PubMedCentralPubMedCrossRef Bertling E, Hotulainen P, Mattila PK, et al. Cyclase-associated protein 1 (CAP1) promotes cofilin-induced actin dynamics in mammalian nonmuscle cells. Mol Biol Cell. 2004;15:2324–34.PubMedCentralPubMedCrossRef
6.
Zurück zum Zitat Shibata R, Mori T, Du W, et al. Overexpression of cyclase-associated protein 2 in multistage hepatocarcinogenesis. Clin Cancer Res. 2006;12:5363–8.PubMedCrossRef Shibata R, Mori T, Du W, et al. Overexpression of cyclase-associated protein 2 in multistage hepatocarcinogenesis. Clin Cancer Res. 2006;12:5363–8.PubMedCrossRef
7.
Zurück zum Zitat 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. 2009;89:425–32.PubMedCrossRef 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. 2009;89:425–32.PubMedCrossRef
8.
Zurück zum Zitat Tan M, Song X, Zhang G, et al. Overexpression of adenylate cyclase-associated protein 1 is associated with metastasis of lung cancer. Oncol Rep. 2013;30:1639–44.PubMed Tan M, Song X, Zhang G, et al. Overexpression of adenylate cyclase-associated protein 1 is associated with metastasis of lung cancer. Oncol Rep. 2013;30:1639–44.PubMed
9.
Zurück zum Zitat 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. 2013;43:856–64.PubMedCrossRef 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. 2013;43:856–64.PubMedCrossRef
10.
Zurück zum Zitat Zhang Q, Wang SY, Nottke AC, et al. Redox sensor CtBP mediates hypoxia-induced tumor cell migration. Proc Natl Acad Sci USA. 2006;103:9029–33.PubMedCrossRef Zhang Q, Wang SY, Nottke AC, et al. Redox sensor CtBP mediates hypoxia-induced tumor cell migration. Proc Natl Acad Sci USA. 2006;103:9029–33.PubMedCrossRef
11.
Zurück zum Zitat Paliwal S, Kovi RC, Nath B, et al. The alternative reading frame tumor suppressor antagonizes hypoxia-induced cancer cell migration via interaction with the COOH-terminal binding protein corepressor. Cancer Res. 2007;67:9322–9.PubMedCrossRef Paliwal S, Kovi RC, Nath B, et al. The alternative reading frame tumor suppressor antagonizes hypoxia-induced cancer cell migration via interaction with the COOH-terminal binding protein corepressor. Cancer Res. 2007;67:9322–9.PubMedCrossRef
12.
Zurück zum Zitat Chen YW, Paliwal S, Draheim K, et al. p19Arf inhibits the invasion of hepatocellular carcinoma cells by binding to C-terminal binding protein. Cancer Res. 2008;68:476–82.PubMedCentralPubMedCrossRef Chen YW, Paliwal S, Draheim K, et al. p19Arf inhibits the invasion of hepatocellular carcinoma cells by binding to C-terminal binding protein. Cancer Res. 2008;68:476–82.PubMedCentralPubMedCrossRef
13.
Zurück zum Zitat Chinnadurai G. CtBP, an unconventional transcriptional corepressor in development and oncogenesis. Mol Cell. 2002;9:213–24.PubMedCrossRef Chinnadurai G. CtBP, an unconventional transcriptional corepressor in development and oncogenesis. Mol Cell. 2002;9:213–24.PubMedCrossRef
14.
Zurück zum Zitat Birts CN, Harding R, Soosaipillai G, et al. Expression of CtBP family protein isoforms in breast cancer and their role in chemoresistance. Biol Cell. 2010;103:1–19.PubMedCentralPubMedCrossRef Birts CN, Harding R, Soosaipillai G, et al. Expression of CtBP family protein isoforms in breast cancer and their role in chemoresistance. Biol Cell. 2010;103:1–19.PubMedCentralPubMedCrossRef
15.
Zurück zum Zitat Tang L, Yang J, Ng SK, et al. Autoantibody profiling to identify biomarkers of key pathogenic pathways in mucinous ovarian cancer. Eur J Cancer. 2010;46:170–9.PubMedCentralPubMedCrossRef Tang L, Yang J, Ng SK, et al. Autoantibody profiling to identify biomarkers of key pathogenic pathways in mucinous ovarian cancer. Eur J Cancer. 2010;46:170–9.PubMedCentralPubMedCrossRef
16.
Zurück zum Zitat Barroilhet L, Yang J, Hasselblatt K, et al. C-terminal binding protein-2 regulates response of epithelial ovarian cancer cells to histone deacetylase inhibitors. Oncogene. 2013;32:3896–903.PubMedCrossRef Barroilhet L, Yang J, Hasselblatt K, et al. C-terminal binding protein-2 regulates response of epithelial ovarian cancer cells to histone deacetylase inhibitors. Oncogene. 2013;32:3896–903.PubMedCrossRef
17.
Zurück zum Zitat Bergman LM, Birts CN, Darley M, et al. CtBPs promote cell survival through the maintenance of mitotic fidelity. Mol Cell Biol. 2009;29:4539–51.PubMedCentralPubMedCrossRef Bergman LM, Birts CN, Darley M, et al. CtBPs promote cell survival through the maintenance of mitotic fidelity. Mol Cell Biol. 2009;29:4539–51.PubMedCentralPubMedCrossRef
18.
Zurück zum Zitat Grooteclaes ML, Frisch SM. Evidence for a function of CtBP in epithelial gene regulation and anoikis. Oncogene. 2000;19:3823–8.PubMedCrossRef Grooteclaes ML, Frisch SM. Evidence for a function of CtBP in epithelial gene regulation and anoikis. Oncogene. 2000;19:3823–8.PubMedCrossRef
19.
Zurück zum Zitat Hildebrand JD, Soriano P. Overlapping and unique roles for C-terminal binding protein 1 (CtBP1) and CtBP2 during mouse development. Mol Cell Biol. 2002;22:5296–307.PubMedCentralPubMedCrossRef Hildebrand JD, Soriano P. Overlapping and unique roles for C-terminal binding protein 1 (CtBP1) and CtBP2 during mouse development. Mol Cell Biol. 2002;22:5296–307.PubMedCentralPubMedCrossRef
20.
Zurück zum Zitat Oesterreich S, Deng W, Jiang S, et al. Estrogen-mediated down-regulation of E-cadherin in breast cancer cells. Cancer Res. 2003;63:5203–8.PubMed Oesterreich S, Deng W, Jiang S, et al. Estrogen-mediated down-regulation of E-cadherin in breast cancer cells. Cancer Res. 2003;63:5203–8.PubMed
21.
Zurück zum Zitat Guan C, Shi H, Wang H, et al. CtBP2 contributes to malignant development of human esophageal squamous cell carcinoma by regulation of p16INK4A. J Cell Biochem. 2013;114:1343–54.PubMedCrossRef Guan C, Shi H, Wang H, et al. CtBP2 contributes to malignant development of human esophageal squamous cell carcinoma by regulation of p16INK4A. J Cell Biochem. 2013;114:1343–54.PubMedCrossRef
22.
Zurück zum Zitat Wang Y, Liu F, Mao F, et al. Interaction with cyclin H/cyclin-dependent kinase 7 (CCNH/CDK7) stabilizes C-terminal binding protein 2 (CtBP2) and promotes cancer cell migration. J Biol Chem. 2013;288:9028–34.PubMedCrossRef Wang Y, Liu F, Mao F, et al. Interaction with cyclin H/cyclin-dependent kinase 7 (CCNH/CDK7) stabilizes C-terminal binding protein 2 (CtBP2) and promotes cancer cell migration. J Biol Chem. 2013;288:9028–34.PubMedCrossRef
Metadaten
Titel
High expression and prognostic role of CAP1 and CtBP2 in breast carcinoma: associated with E-cadherin and cell proliferation
verfasst von
Xiancheng Liu
Ninghua Yao
Jing Qian
Huiwei Huang
Publikationsdatum
01.03.2014
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 3/2014
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0878-7

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