Livin promotes tumor progression through YAP activation in ovarian cancer

Livin 通过激活 YAP 促进卵巢癌中的肿瘤进展

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作者:Jianhua Gao, Wei Han, Yanan He, Jun Zhou, Jintian Miao, Guangmei Zhang

Abstract

Ovarian cancer is a gynecological malignant tumor with a high morbidity. Livin is a novel member of the inhibitor of apoptosis protein family, which is expressed in various malignant tumors and is suggested to be a poor prognostic factor. However, the prognostic significance of Livin and the molecular mechanisms by which Livin promotes ovarian cancer progression are poorly understood. In this study, the upregulation of Livin was confirmed both in primary specimens from ovarian cancer patients and in ovarian cancer cell lines compared to normal controls in vitro. Overexpression of specific Livin transcripts promoted cell growth and migration in vitro, while knockdown of Livin expression suppressed these cellular processes. These effects of the Livin gene were also demonstrated in a xenograft mouse model. Mechanistic studies further revealed that Livin promotes the proliferation and invasion of ovarian cancer cells by activating the transcriptional coactivator YAP, a critical component of the Hippo signaling pathway. Furthermore, we revealed that inhibition of YAP by short-hairpin RNA prevents the growth and invasion of ovarian cancer cells in vivo and in vitro. Therefore, Livin may be a potential novel therapeutic target for the treatment of ovarian cancer.

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