Annexin A2 interacting with ELMO1 regulates HCC chemotaxis and metastasis.

AIMS

SDF-1α induced chemotaxis plays an important role in hepatocellular carcinoma metastasis. CXCR4 stimulated by SDF-1α/CXCL12 triggers heterotrimeric G proteins activation, which regulate migration and chemotaxis of hepatocellular carcinoma cells. The pathways linking the chemokine GPCR/Gi signaling to actin polymerization for migration of cancer cells are not known.

MATERIALS AND METHODS

Through would healing assay, chemotaxis assay, F-actin polymerization assay, confocal assay, immunohistochemical assay, protein identification and coimmunoprecipitation assay, we detected the role and mechanisms of Annexin A2 in hepatocellular carcinoma.

KEY FINDINGS

In the present study, we firstly investigated the role of Annexin A2 in HepG2 cell chemotaxis and metastasis. Immunohistochemical analysis showed that Annexin A2 was highly expressed in hepatocellular carcinoma tissues. Its expression was closely associated with lymph node and distant metastasis. Knockdown Annexin A2 impaired cancer cell chemotaxis. Co-immunoprecipitation results showed an interaction between Annexin A2 and ELMO1. CXCL12 triggers an ELMO1-dependent membrane translocation of Annexin A2.

SIGNIFICANCE

Taken together, our results indicated an important role of Annexin A2 in hepatocellular carcinoma tissues metastasis and revealed a novel molecular mechanism of its activation.