Department of Gynecology and Obstetrics, Guangzhou Institute of Obstetrics & Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510150, PR China.
Department of Pathology, Central Laboratory of Third Affiliated Hospital of Guangzhou Medical University, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510150, PR China.
Biomed Pharmacother. 2019 Jul;115:108939. doi: 10.1016/j.biopha.2019.108939. Epub 2019 May 9.
Family with sequence similarity 83 member B (FAM83B) has been recently identified as an oncogene involved in the development of various human cancers. However, the role of FAM83B in endometrial cancer tumorigenesis and metastasis is unclear. In this study, we found that the expression of FAM83B was upregulated in endometrial cancer tissues and cell lines. FAM83B expression in endometrial cancer tissues was significantly higher than that in normal tissues and higher FAM83B expression was closely related to poorly survival rate according to TCGA analysis. Moreover, FAM83B expression was correlated with International Federation of Gynecology and Obstetrics (FIGO)stage and myometrial invasion but had no significant correlation with age or histological grade. FAM83B knockdown inhibited endometrial cancer cell proliferation, migration, and invasion arrested the cell cycle at the G1/S stage and promoted apoptosis. FAM83B knockdown also inhibited endometrial cancer growth and lung metastasis in vivo. FAM83B knockdown silenced the PI3K/AKT/mTOR pathway and promoted autophagy. Furthermore, activation of the PI3K/AKT/mTOR pathway reversed FAM83B knockdown-induced autophagy promotion and inhibition of proliferation, migration, and invasion in endometrial cancer cells. Taken together, these results indicate that FAM83B promotes endometrial cancer cell proliferation and metastasis by inhibiting autophagy via activating the PI3K/AKT/mTOR pathway.
家族与序列相似性 83 成员 B（FAM83B）最近被鉴定为一种参与多种人类癌症发展的癌基因。然而，FAM83B 在子宫内膜癌肿瘤发生和转移中的作用尚不清楚。在这项研究中，我们发现 FAM83B 在子宫内膜癌组织和细胞系中的表达上调。根据 TCGA 分析，FAM83B 在子宫内膜癌组织中的表达明显高于正常组织，并且高表达 FAM83B 与生存率降低密切相关。此外，FAM83B 的表达与国际妇产科联合会（FIGO）分期和肌层浸润有关，但与年龄或组织学分级无显著相关性。FAM83B 敲低抑制子宫内膜癌细胞增殖、迁移和侵袭，将细胞周期阻滞在 G1/S 期，并促进细胞凋亡。FAM83B 敲低还抑制了体内子宫内膜癌的生长和肺转移。FAM83B 敲低沉默了 PI3K/AKT/mTOR 通路并促进了自噬。此外，激活 PI3K/AKT/mTOR 通路逆转了 FAM83B 敲低诱导的自噬促进以及对子宫内膜癌细胞增殖、迁移和侵袭的抑制作用。综上所述，这些结果表明 FAM83B 通过激活 PI3K/AKT/mTOR 通路抑制自噬来促进子宫内膜癌细胞的增殖和转移。
