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Anxa2 Plays a Critical Role in Enhanced Invasiveness of the Multidrug Resistant Human Breast Cancer Cells

Fei Zhang^†, Lin Zhang^†, Bin Zhang^†, Xiyin Wei^†, Yi Yang^†, Robert Z. Qi^‡, Guoguang Ying^†, Ning Zhang*^§ and Ruifang Niu*^†

Key Laboratory of Breast Cancer Prevention and Treatment, Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China, Department of Biochemistry, The Hong Kong University of Science and Technology, Hong Kong, P.R. China, and Research Center of Basic Medical Science, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, P.R. China

J. Proteome Res., 2009, 8 (11), pp 5041–5047

DOI: 10.1021/pr900461c

Publication Date (Web): September 18, 2009

* To whom correspondence should be addressed. Ning Zhang, Tianjin Medical University, Research Center of Basic Medical Sciences & Cancer Institute and Hospital, Tianjin, 300060 China; e-mail, nzhangchina@yahoo.com. Ruifang Niu, Tianjin Medical University Cancer Institute and Hospital, Tianjin. 300060, China; e-mail, Niurf1982@yahoo.com.cn., †

Key Laboratory of Breast Cancer Prevention and Treatment, Tianjin Medical University Cancer Institute and Hospital.

, ‡

The Hong Kong University of Science and Technology.

, §

Research Center of Basic Medical Science, Tianjin Medical University Cancer Institute and Hospital.

Abstract

Multidrug resistance (MDR) is the major cause of failure in cancer chemotherapy. Recent reports even suggest that MDR is associated with elevated invasion and metastasis of tumor cells. In the current study, we used a proteomic approach to identify genes that play an important role in MDR induced cell migration. 2D-PAGE and MALDI-TOF/MS-based proteomics approach were used to separate and identify differentially expressed proteins between MCF-7 and MCF-7/ADR, a p-glycoprotein-overexpressing adriamycin-resistance breast cancer cell line. Annexin a2 (Anxa2) was identified as highly expressed in MCF-7/ADR cells, but not in MCF-7 cells. Small interference RNA-mediated gene suppression demonstrated that Anxa2 was required for enhanced cell proliferation and invasion of the MCF-7/ADR cells. Down-regulation of Anxa2 alone was not sufficient to revert the cell sensitivity to adriamycin, suggesting that Anxa2 was not required for MDR phenotype. Taken together, our results showed that expression of Anxa2 is enhanced when cancer cells, MCF-7, acquired drug resistance and it plays an essential role in MDR-induced tumor invasion.

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