CD24 induces the invasion of cholangiocarcinoma cells by upregulating CXCR4 and increasing the phosphorylation of ERK1/2

Cholangiocarcinoma is a malignant biliary tract tumor with an extremely poor prognosis. CD24 expression has been linked to the aggressiveness of cholangiocarcinoma cells and the adverse prognosis of cholangiocarcinoma patients. In the present study, the underlying mechanism of aggressive CD24(+) cholangiocarcinoma cell behavior was elucidated. The magnetic-activated cell sorting system was used to isolate CD24(+) and CD24(−) cell populations from RMCCA1 cholangiocarcinoma cells. Using a human tumor metastasis PCR array, it was observed that numerous tumor-associated genes were upregulated in the CD24(+) cells, including CXC chemokine receptor type 4 (CXCR4). In addition, an intracellular signaling array demonstrated the activation of extracellular signal-regulated kinase (ERK)1/2, which is downstream of the CXCR4 signaling cascade, in the CD24(+) cells. Inhibition of CXCR4 or ERK1/2 significantly inhibited the motility and invasiveness of the CD24(+) cells. The present study indicates that CXCR4 and ERK1/2 are induced by CD24 and that these proteins are associated with cholangiocarcinoma cell invasion.