Open AccessFAM 134B induces tumorigenesis and epithelial‐to‐mesenchymal transition via Akt signaling in hepatocellular carcinoma
Author(s) -
Zhang Zhaoqi,
Chen Jin,
Huang Wanqiu,
Ning Deng,
Liu Qiumeng,
Wang Chao,
Zhang Long,
Ren Li,
Chu Liang,
Liang Huifang,
Fan Haining,
Zhang Bixiang,
Chen Xiaoping
Publication year - 2019
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12429
Subject(s) - hepatocellular carcinoma , epithelial–mesenchymal transition , carcinogenesis , cancer research , protein kinase b , signal transduction , mesenchymal stem cell , transition (genetics) , biology , chemistry , microbiology and biotechnology , medicine , cancer , gene , genetics
Fam134b (JK‐1, RETREG1) was first identified as an oncogene in esophageal squamous cell carcinoma. However, the roles of FAM 134B during tumorigenesis of hepatocellular carcinoma ( HCC ) and in epithelial‐to‐mesenchymal transition ( EMT ) were previously unclear. In this study, we investigated the function of FAM 134B in HCC and the related tumorigenesis mechanisms, as well as how FAM 134B induces EMT . We detected the expression of FAM 134B in a normal hepatic cell line, HCC cell lines, fresh specimens, and a HCC tissue microarray. A retrospective study of 122 paired HCC tissue microarrays was used to analyze the correlation between FAM 134B and clinical features. Gain‐ and loss‐of‐function experiments, rescue experiments, Akt pathway activator/inhibitors, nude mice xenograft models, and nude mice lung metastasis models were used to determine the underlying mechanisms of FAM 134B in inducing tumorigenesis and EMT in vitro and in vivo . The expression level of FAM 134B was highly elevated in HCC , as compared with that in normal liver tissues and normal hepatic cells. Overexpression of FAM 134B was significantly associated with tumor size ( P = 0.025), pathological vascular invasion ( P = 0.026), differentiation grade ( P = 0.023), cancer recurrence ( P = 0.044), and portal vein tumor thrombus ( P = 0.036) in HCC . Patients with high expression of FAM 134B had shorter overall survival and disease‐free survival than patients with non‐high expression of FAM 134B. Furthermore, knockdown of FAM 134B with sh RNA s inhibited cell growth and motility, as well as tumor formation and metastasis in nude mice, all of which were promoted by overexpression of FAM 134B. Our study demonstrated that Fam134b is an oncogene that plays a crucial role in HCC via the Akt signaling pathway with subsequent glycogen synthase kinase‐3β phosphorylation, accumulation of β‐catenin, and stabilization of Snail, which promotes tumorigenesis, EMT , and tumor metastasis in HCC .