FAM64A contributes to ovarian cancer proliferation and metastasis by suppressing TWIST1 ubiquitination degradation.

Abstract

Ovarian cancer is among the most common cancers among gynecological malignancies. FAM64A is associated with various cancer progressions, but its function and mechanism in ovarian cancer remain unclear. We analyzed and examined the expression of FAM64A in ovarian cancer cells and tissues. The proliferation, migration, and invasion were assessed by knocking down and overexpressing FAM64A in A2780 and SKOV3 cells, respectively. Bioinformatics combined with molecular experiments validated the molecular mechanism of FAM64A. The xenograft tumor model and lung metastasis model were created to explore the impact of FAM64A on tumor growth and metastasis of the nude mice. To evaluate the relative signaling molecule expression, immunohistochemistry (IHC) and Western blot assays were conducted. FAM64A was up-regulated in ovarian cancer tissues and cells and demonstrated to promote the proliferation, migration, and invasion of A2780 and SKOV3 cells in vitro. Bioinformatics and western blot assay indicated that FAM64A could regulate EMT-related transcription factor TWIST1 by suppressing TWIST1 ubiquitination and degradation via the E3 ubiquitin ligase STUB1. Moreover, the Knockdown of FAM64A inhibited tumor growth of xenograft tumor mice and lung metastasis in vivo. FAM64A exerts its oncogene function via regulating TWIST1 ubiquitination and degradation, indicating that FAM64A may provide a promising therapeutic target for the treatment of ovarian cancer.