Coronin 6 promotes hepatocellular carcinoma progression by enhancing canonical Wnt/beta-catenin signaling pathway

Abstract

Hepatocellular carcinoma (HCC), which is one of the most commonly diagnosed cancers, accounts for a large majority of cancer-related mortality worldwide. Although various genes have already been found to play vital regulatory roles in HCC progression, the pathological mechanism is still not well-understood. In this study, we find Coronin 6 (CORO6) is highly expressed in HCC samples with higher grades and is correlated with poor patient outcomes. CORO6 depletion significantly impairs the cell survival, migratory and invasive abilities of HCC cells. Pathway analysis and reporter assay reveal that Wnt signaling is enhanced by CORO6 in HCC cells. Moreover, WNT10B is identified as a target gene of CORO6. In vivo experiments suggest that knockdown of CORO6 inhibited the tumor growth. Importantly, expression of the key WNT target genes that are involved in cell cycle regulation and tumorigenesis, is downregulated in the absence of CORO6. Collectively, our results uncover a novel function of CORO6 in HCC progression and prove that the activation of WNT signaling is responsible for the tumor-promoting role of CORO6, which may offer a new target for therapeutic gain of treating HCC.