Open AccessTCF19 enhances cell proliferation in hepatocellular carcinoma by activating the ATK/FOXO1 signaling pathway
Author(s) -
Chenglong Zeng,
Sengwang Fu,
Wenhua Feng,
Junfei Zhao,
F. X. Li,
Peng Gao
Publication year - 2019
Publication title -
neoplasma
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.628
H-Index - 50
eISSN - 1338-4317
pISSN - 0028-2685
DOI - 10.4149/neo_2018_171227n845
Subject(s) - cancer research , hepatocellular carcinoma , foxo1 , cell growth , protein kinase b , carcinogenesis , cell cycle , flow cytometry , cell , cyclin d1 , retinoblastoma protein , biology , pi3k/akt/mtor pathway , metastasis , signal transduction , immunology , cancer , microbiology and biotechnology , genetics
Hepatocellular carcinoma (HCC) is one of the most lethal malignancies because of its complexity, high metastasis, recurrence and limited treatment options. Reports state that transcription factor 19 (TCF19) is related to the susceptibility to chronic HBV infection and that it strongly increases the risk of HCC occurrence, but its molecular mechanisms remain unknown. This study analyzed the datasets and confirmed that TCF19 is significantly increased in HCC cell lines and tissues. MTT and colony formation assay revealed that TCF19 over-expression enhances cell proliferation and tumorigenesis. Flow cytometry assay then determined that TCF over-expression helps HCC cell G1/S phase transition, and further research showed that TCF19 up-regulation inhibits p57Kip2, p21Cip1 and p27Kip1 cell cycle suppressors, enhances the expression of cyclin D1 expression and simulates retinoblastoma (Rb), FOXO1 and AKT phosphorylation. In addition, AKT and FOXO1 inhibitors suppress the TCF19 effect on cell proliferation. This demonstrates that AKT/FOXO1 signaling is essential for TCF19 influence on HCC progression, and our combined results suggest that crucial links between TCF19 and HCC can provide a novel target for hepatocellular carcinoma treatment.