Annexin A1 Is a Potential Prognostic Marker for, and Enhances the Metastasis of, Cholangiocarcinoma

Document Type : Research Articles


1 Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.

2 Center for Translational Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.

3 Medical Technology Program, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80161, Thailand.

4 Department of Biochemistry, Faculty of Science, Prince of Songkla University, Songkhla 90110, Thailand.

5 Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection & Graduate School of Medical Sciences, Kumamoto University, 860-0811, Japan.


Objective: Annexin A1 (ANXA1) is a calcium-dependent phospholipid-binding protein which contributes to proliferation, cancer progression and metastasis. Overexpression of ANXA1 is closely associated with metastasis in numerous types of cancer. Cholangiocarcinoma (CCA) is a bile-duct cancer which has high rates of metastasis. Previously, we demonstrated up-regulation of ANXA1 in a highly metastatic CCA cell line (KKU-213AL5). Here, we investigated the functions of ANXA1 in the progression of CCA cell lines and evaluated its clinical impacts in human CCA tissues.  Methods: Effects of ANXA1 on metastatic potential of CCA cell lines were evaluated using cell-proliferation, clonogenic, migration and invasion assays. The expression of ANXA1 in 44 intrahepatic human CCA tissues was investigated using immunohistochemistry (IHC). The association of ANXA1 with clinicopathological features of CCA patients was analyzed. Results: Silencing of ANXA1 expression using siRNA significantly decreased cell proliferation, colony formation, cell migration and invasion in the KKU-213AL5 cell line. IHC results showed low expression of ANXA1 in normal bile ducts in the non-tumor area. In contrast, high expression of ANXA1 in human CCA tissues was associated with advanced tumor stage, tumor size and presence of lymph-node metastasis. Conclusion: These findings strongly imply that ANXA1 contributes to the progression of CCA. ANXA1 can serve as a potential prognostic marker for CCA. Ablation of ANXA1 action may be an alternative strategy to prevent metastasis of CCA.


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