Actin‐like 6A predicts poor prognosis of hepatocellular carcinoma and promotes metastasis and epithelial‐mesenchymal transition

Abstract

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide because of metastasis. Epithelial‐mesenchymal transition (EMT) is widely considered to be crucial to the invasion‐metastasis cascade during cancer progression. Actin‐like 6A (ACTL6A) is initially verified important for cell proliferation, differentiation, and migration. In this study, we find that ACTL6A plays an essential role in metastasis and EMT of HCC. ACTL6A expression is up‐regulated in HCC cells and tissues. A high level of ACTL6A in HCCs is correlated with aggressive clinicopathological features and is an independent poor prognostic factor for overall and disease‐free survival of HCC patients. Ectopic expression of ACTL6A markedly promotes HCC cells migration, invasion, as well as EMT in vitro and promotes tumor growth and metastasis in the mouse xenograft model. Opposite results are observed when ACTL6A is knocked down. Mechanistically, ACTL6A promotes metastasis and EMT through activating Notch signaling. ACTL6A knockdown has the equal blockage effect as the Notch signaling inhibitor, N‐[N‐(3,5‐difluorophenacetyl)‐L‐alanyl]‐S‐phenylglycine t‐butylester, in HCC cells. Further studies indicate that ACTL6A might manipulate SRY (sex determining region Y)‐box 2 (SOX2) expression and then activate Notch1 signaling. Conclusions: ACTL6A promotes metastasis and EMT by SOX2/Notch1 signaling, indicating a prognostic biomarker candidate and a potential therapeutic target for HCC. (Hepatology 2016;63:1256–1271)

Holliday junction–recognizing protein promotes cell proliferation and correlates with unfavorable clinical outcome of hepatocellular carcinoma

“…This study confirmed that multi-tumors ( P =0.016), poor differentiation ( P =0.047), BCLC stage ( P =0.006), and TNM stage ( P =0.004) all were significantly associated with unfavorable prognosis of HCC, which was in agreement with the previous reports 16–18. Notably, HJURP expression was also verified to be a prognostic factor.…”

The Progress of Diallyl Disulfide in Anti-Cancer

“…The cells with EMT are present certain anti-apoptotic activity and drug resistance [89]. The signaling pathways involved in EMT include TGF-β, Wnt, Hedgehog, Notch, ILK, and uPAR (urokinase-type plasminogen activator receptor) [90][91][92][93][94][95]. A recent study has revealed that DADS induces the reversal of the EMT and inhibits cell growth by inactivating the β-catenin signaling pathway in breast cancer cells [96].…”

Overexpression of SMYD3 Is Predictive of Unfavorable Prognosis in Hepatocellular Carcinoma

“…There are about 782,500 new HCC cases and 745,500 HCC-related deaths worldwide in 2012, which is more severe in China (Xiao et al 2016). The curative treatments of HCC include surgical resection, tumor ablation and liver transplantation.…”