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α-Actinin-4 induces the epithelial-to-mesenchymal transition and tumorigenesis via regulation of Snail expression and β-catenin stabilization in cervical cancer

Oncogene volume 35, pages 5893–5904 (2016)Cite this article

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Abstract

α-Actinin-4 (ACTN4) is frequently amplified and overexpressed in various cancers. Although ACTN4 functions in cancer cell migration and invasion, the roles of ACTN4 during the epithelial-to-mesenchymal transition (EMT) and cervical cancer tumorigenesis are unknown. In this study, we investigated the function of ACTN4 in the progression of cervical cancer and the mechanisms of EMT and tumorigenesis induced by ACTN4. We found that ACTN4 induced EMT by upregulating Snail, which was dependent on the Akt signaling pathway in cervical cancer. ACTN4 induced cell migration and invasion through Snail-mediated matrix metalloproteinase-9 expression. ACTN4 expression level was correlated with stabilization of β-catenin. Accumulatioin of β-catenin owing to ACTN4 induced tumorigenesis via upregulation of genes involved in cell proliferation, including cyclin D1 and c-myc. ACTN4 knockdown reduced cervical cancer cell proliferation and tumor formation in vivo. The expression level of ACTN4 is highly elevated in human cervical tumors, compared with that in normal cervical tissues. ACTN4-overexpressing MDCK cells induced tumor formation and metastatic nodules in nude mice. Our findings indicate that ACTN4 promotes EMT and tumorigenesis by regulating Snail expression and the Akt pathway in cervical cancer. We propose a novel mechanism for EMT and tumorigenesis in cervical cancer.

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Acknowledgements

This work was supported by Basic Science Research Program (NRF-2014R1A2A2A01002826) and Tunneling Nanotube Research Center (NRF-2015R1A5A1009024) through the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) and the Korea University Grant.

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  1. Division of Life Sciences, Korea University, Seoul, South Korea

    H-T An, S Yoo & J Ko

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Correspondence to J Ko.

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An, HT., Yoo, S. & Ko, J. α-Actinin-4 induces the epithelial-to-mesenchymal transition and tumorigenesis via regulation of Snail expression and β-catenin stabilization in cervical cancer. Oncogene 35, 5893–5904 (2016). https://doi.org/10.1038/onc.2016.117

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