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Annexin II promotes invasion and migration of human hepatocellular carcinoma cells in vitro via its interaction with HAb18G/CD147 Pu Zhao,1,4 Wei Zhang,2,4 Juan Tang,1 Xiao-Kui Ma,1 Jing-Yao Dai,2 Yong Li,1 Jian-Li Jiang,1,3 Si-He Zhang1,3 and Zhi-Nan Chen1,3 1Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer Biology, State Key Discipline of Cell University, Fourth Military Medical University, Xi’an, China; 2Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China (Received June 17, 2009 ? Revised October 14, 2009 ? Accepted October 22, 2009/Online publication December 25, 2009)3To whom correspondence should be addressed. E-mail: jiangjl@fmmu.edu.cn, zshzq@fmmu.edu.cn and znchen@fmmu.edu.cn 4These authors contributed equally to this work.HAb18G ?CD147, a member of the immunoglobulin family enriched on the surface of tumor cells, is reported to be correlated with invasion, metastasis, growth, and survival of malignant cells. Here, we found that annexin II, a 36-kDa Ca2+- and phospholipid-binding protein and in vivo substrate for tyrosine kinase and PKC, is a new interaction protein of HAb18G ?CD147 in human hepatocellular car- cinoma (HCC) cells. In the present study, we explored the unclear role of annxin II in HCC invasion and migration and the interaction effects between HAb18G ?CD147 and annexin II. Our data show that downregulation of annexin II in HCC cells significantly decreased the secretion of MMP, migration ability, and invasive potential, and affected the cytoskeleton rearrangement of tumor cells. The MMP-2 level and invasive potential of HCC cells were regulated by both annexin II and HAb18G ?CD147. Also, interaction effects exist between the two molecules in tumor progression, including MMP-2 production, migration, and invasion. These results suggest that annexin II promotes the invasion and migration of HCC cells in vitro, and annexin II and HAb18G ?CD147 intera