Open AccessID1 overexpression promotes HCC progression by amplifying the AURKA/Myc signaling pathway
Author(s) -
Man Wu,
Yuhong Zhou,
Chengming Fei,
Tian-Yi Chen,
Xin Yin,
Lan Zhang,
Zhenggang Ren
Publication year - 2020
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo.2020.5092
Subject(s) - cancer research , oncogene , downregulation and upregulation , biology , cell cycle , signal transduction , gene silencing , kinase , hepatocellular carcinoma , foxm1 , cancer , microbiology and biotechnology , gene , genetics , biochemistry
Hepatocellular carcinoma (HCC) is the fourth most common cancer type worldwide, with a poor prognosis and high mortality rate. The aim of the present study was to investigate the mechanisms underlying HCC progression to potentially benefit the development of effective therapies for advanced HCC. The present study reported a novel mechanism that promotes the HCC malignant phenotype, in which the inhibitor of differentiation 1 (ID1) activates the aurora kinase A (AURKA)/Myc signaling pathway. Specifically, a high expression of ID1 promoted a highly malignant phenotype of HCC cells that exhibit enhanced metastatic ability and drug resistance. However, the effects of ID1 were markedly reversed by the AURKA inhibitor VX689 and the Myc inhibitor 10058‑F4. Further studies demonstrated that ID1 competitively binds with anaphase‑promoting complex/cyclosome Cdh1 (APC/CCdh1), which is responsible for ubiquitination‑mediated AURKA protein degradation, resulting in upregulation of AURKA. Increased AURKA expression subsequently enhanced Myc expression at both transcriptional and post‑transcriptional level, leading to amplification of the Myc oncogenic signaling pathway. This novel ID1/AURKA/Myc axis could be a promising therapeutic target for the development of effective therapeutic strategies for advanced HCC.