Recent studies have shown that dysregulation of ANXA1 expression are associated with tumorigenesis. Overexpression of ANXA1 protein is found in a wide variety of human tumors, such as breast 10, liver 11, pancreatic cancer14 and glial tumors15. In contrast, reduced levels of ANXA1 protein expression have been reported in ESCC4, 5, gastric6, breast7, head and neck SCC8 and prostate cancer9. No previous study on ANXA1 protein expression has been reported in the cancer of oral cavity. Furthermore, although alterations in annexin expression in different types of tumors have been described, no correlation has been established between ANXA1 and overall patient survival yet.

ANXA1 is a major cellular substrate of the oncogenic tyrosine kinases such as EGF receptor and hepatocyte growth factor (HGF) receptor, c-met.

Previously, we have shown that expression of HGF and c-met is significantly associated with the progression of OSCC in Taiwan. Kermorgant et al.

recently showed that PKC controls HGF-dependent c-met traffic, signaling and cell migration. Prior study indicate that the mitogen phorbol-12-myristate 13-acetate (PMA) induced ANXA1 nuclear translocation in a PKCdelta-dependent manner and ANXA1 nuclear translocation may participate in the regulation of cellular proliferation and the differentiation. However, it is not known whether HGF can induce ANXA1 nuclear translocation or not and how this relates to the pathogenesis of oral SCC. In this study we aimed to investigate whether HGF induced the translocation of ANXA1 protein to the nucleus in OSCC cells and the role(s) of ANXA1 nuclear localization in the carcinogenesis of OSCC using an immunohistochemical technique. The data suggest a novel mechanism for HGF-induced ANXA1 protein nuclear translocation that may play an important role in the pathogenesis and prognosis in oral SCCs.