Sec62 Promotes Early Recurrence of Hepatocellular Carcinoma Through Activating Integrinα/CAV1 Signaling

Abstract

Background: Postsurgical recurrence within 2 years is the major cause of poor survival of hepatocellular carcinoma (HCC) patients. However, the molecular mechanism underlying HCC recurrence remains unclear. Here, we distinguish the function and mechanism of Sec62 in promoting HCC recurrence. Methods: The correlation between Sec62 and early recurrence was demonstrated in 60 HCC samples from a prospective study. HCC cells with Sec62 knockdown (Sec62KD) or overexpression (Sec62OE) were used to determine the potential of Sec62 in cell migration in vitro. Microarray analysis comparing Sec62KD or Sec62OE to their control counterparts was used to explore the mechanisms of Sec62-induced recurrence. A luciferase-labelled orthotopic nude mouse model of HCC with Sec62KD or Sec62OE was used to validate the potential of Sec62 in early HCC recurrence in vivo. Findings: High expression of Sec62 was positively correlated with surgical recurrence in clinical HCC samples. Multivariate analysis revealed that Sec62 was an independent prognostic factor for early recurrence in postoperative HCC patients. Moreover, Sec62 promoted migration and invasion of HCC cells in vitro and postsurgical recurrence in vivo. Mechanically, integrinα/CAV1 signalling was identified as one of the targets of Sec62 in cell movement. Overexpression of integrinα partially rescued the Sec62 knockdown-induced inhibition of cell migration. Interpretation: Sec62 is a potentially prognostic factor for early recurrence in postoperative HCC patients and promotes HCC metastasis through integrinα/CAV1 signalling. Sec62 might be an attractive drug target for combating HCC postsurgical recurrence. Funding Statement: This work was supported by the National Nature Science Foundation of China (grant number: 81473484) and the Nature Science Foundation of Shanghai (grant number: 14ZR1408400). Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: The animal protocols were performed in agreement with the SIBS Guide for the Care and Use of Laboratory Animals and were approved by the Animal Ethics Committee of Zhongshan Hospital, Fudan University.