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ANXA3

annexin A3;ANXA3;annexin A3

35-alpha calcimedin|Annexin III (lipocortin III)|PAP-III|annexin III (lipocortin III, 1,2-cyclic-inositol-phosphate phosphodiesterase, placental anticoagulant protein III, calcimedin 35-alpha)|annexin-3|calcimedin 35-alpha|inositol 1,2-cyclic phosphate 2-

4q21.21

protein-coding

OBJECTIVE: Annexins are a family of intracellular proteins that bind membrane phospholipids in a Ca(2+) concentration-dependent manner. Several annexins play important roles during tumor progression. However, little is known about the clinical implications and biological functions of Annexin A3 in breast cancer. METHODS: Using immunohistochemistry, we analyzed 60 breast cancers for the levels of annexin A3 and investigated the correlation of its expression change with patient's survival via Kaplan-Meier survival analysis. Furthermore, via knockdown of Annexin A3 expression in breast cancer cells with special siRNA, the role of Annexin A3 in the proliferation and apoptosis of breast cancer cells was examined. RESULTS: Annexin A3 was expressed at higher level in breast cancer than that in normal breast tissue. The expression of Annexin A3 in human breast carcinoma closely correlated with tumor size and axillary lymph node metastasis. Kaplan-Meier survival analysis revealed a significant inverse correlation between strong Annexin A3 expression and overall patient survival. Moreover, Annexin A3 overexpression was inversely associated with Bax staining and the apoptosis index. Annexin A3 small interfering RNA in MCF-7 and MDA-MB-435 could inhibit cell proliferation, decrease Bcl-2 mRNA and protein expression, and increase Bax mRNA and protein expression. CONCLUSION: Our findings indicated that Annexin A3 might be a novel and potential prognostic marker for patients with breast cancer and be involved in regulating apoptosis by affecting Bcl-2/Bax balance.

Lymph node status is a strong predictor of outcome for lung adenocarcinoma (AdC) patients. To explore novel potential protein markers for predicting lymph node metastasis of lung AdC, differential proteomic analysis on microdissected cancer cells from primary lung AdC and matched lymph node (LN) metastatic tissues by laser capture microdissection (LCM) was conducted using two-dimensional differential in-gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS). Annexins including annexin-1, annexin-2 and annexin-3 were identified and found to be overexpressed in matched LN metastatic tissues compared to primary lung AdC. Furthermore, differential expression levels of the three annexins were evaluated in paraffin-embedded 188 primary lung AdC tissues and 65 matched positive lymph node specimens using immunohistochemistry. High expression of annexin-1, annexin-2, and annexin-3 was all frequently observed in matched positive lymph node tissues compared to primary lung AdC. In primary lung AdC, expression levels of the three annexins in primary lymph node-positive AdC tissues were higher than primary lymph node-negative AdC tissues. Multivariate logistic regression analysis indicated annexin-1, annexin-2, and annexin-3 were all significant risk factors for lymph node metastasis. Furthermore, statistical analysis indicated that the concomitant expression of annexin-1/annexin-2, annexin-1/annexin-3, or annexin-2/annexin-3 and combined expression of all three markers had stronger correlation with lymph node metastasis. Our results suggest that annexin-1, annexin-2, and annexin-3 are identified as potential biomarkers associated with lymph node metastasis in lung AdC.

Annexin family proteins are a well-known multigene family of Ca(2+)-regulated phospholipid- and membrane-binding proteins. As one of the annexin family genes/proteins, accumulated researches have begun to reveal that annexin A3 (Anxa3) exhibits important roles in tumor development, metastasis and drug resistance. The summarized research evidences in recent years indicate Anxa3 might specifically functionalize either as a tumor suppressor or as a tumor promoter candidate for different cancers depending on the types of tumor cells and tissues. The up-regulation of Anxa3 was found to be correlated with enhanced drug resistance of ovarian cancer, to promote the developments of colorectal adenocarcinoma and pancreatic carcinoma, and to facilitate the metastases of lung adenocarcinoma and hepatocarcinoma; meanwhile, the decreased Anxa3 expressions was negatively correlated with the developments of prostatic carcinoma and renal carcinoma. It is conceivable that Anxa3 could be regarded as a target for therapeutic intervention and a biological indicator for tumor development, invasion and metastasis as well as for the prognosis of tumor patients.