Kindlin-2 controls sensitivity of prostate cancer cells to cisplatin-induced cell death

Gong, Xiaowei; An, Zhengwen; Wang, Yunling; Guan, Lizhao; Fang, Weigang; Strömblad, Staffan; Jiang, Yong; Zhang, Hongquan

doi:10.1016/j.canlet.2010.08.003

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Volume 299, Issue 1 , Pages 54-62, 18 December 2010

Kindlin-2 controls sensitivity of prostate cancer cells to cisplatin-induced cell death

Xiaowei Gong
- Karolinska Institutet, Center for Biosciences, Department of Biosciences and Nutrition, SE-141 83 Huddinge, Sweden
- Department of Pathophysiology and Key Laboratory of Proteomics of Guangdong Province, Southern Medical University, Guangzhou 510515, China
- Contributed equally to this study.
Zhengwen An
- Karolinska Institutet, Center for Biosciences, Department of Biosciences and Nutrition, SE-141 83 Huddinge, Sweden
- Contributed equally to this study.
Yunling Wang
- Karolinska Institutet, Center for Biosciences, Department of Biosciences and Nutrition, SE-141 83 Huddinge, Sweden
Lizhao Guan
- Key Laboratory of Carcinogenesis and Translational Research, The Ministry of Education, Laboratory of Molecular Cell Biology and Tumor Biology, Department of Histology, Embryology and Pathology, Peking University Health Science Center, Beijing 100191, China
Weigang Fang
- Key Laboratory of Carcinogenesis and Translational Research, The Ministry of Education, Laboratory of Molecular Cell Biology and Tumor Biology, Department of Histology, Embryology and Pathology, Peking University Health Science Center, Beijing 100191, China
Staffan Strömblad
- Karolinska Institutet, Center for Biosciences, Department of Biosciences and Nutrition, SE-141 83 Huddinge, Sweden
Yong Jiang
- Department of Pathophysiology and Key Laboratory of Proteomics of Guangdong Province, Southern Medical University, Guangzhou 510515, China
- Correspondence to: Department of Pathophysiology, Southern Medical University, Guangzhou 510515, China. Tel.: +86 20 61648231.
Hongquan Zhang
- Karolinska Institutet, Center for Biosciences, Department of Biosciences and Nutrition, SE-141 83 Huddinge, Sweden
- Key Laboratory of Carcinogenesis and Translational Research, The Ministry of Education, Laboratory of Molecular Cell Biology and Tumor Biology, Department of Histology, Embryology and Pathology, Peking University Health Science Center, Beijing 100191, China
- Correspondence to: Department of Biosciences and Nutrition, Karolinska Institutet, SE-141 83 Stockholm, Sweden. Tel.: +46 8 608 9267; fax: +46 8 608 1501.

Received 2 June 2010; received in revised form 5 August 2010; accepted 9 August 2010. published online 02 September 2010.

Abstract

Resistance to anticancer drugs is often observed in prostate cancer therapy. Kindlin-2 was recently found overexpressed during cancer progression. In this study, we examined the functional role of Kindlin-2 in cisplatin-induced prostate cancer cell death. Kindlin-2 was highly expressed in the androgen-insensitive (PC-3 and DU-145), but not in the androgen-sensitive cell lines (e.g., LNCaP). Overexpression of Kindlin-2 in LNCaP protected the cells from cisplatin-induced death, while Kindlin-2 knock-down in PC-3 cells enhanced cisplatin sensitivity. Mechanistically, Kindlin-2 regulation of the anti-apoptotic Bcl-xL may explain the increased cell death in the absence of Kindlin-2. Taken together, Kindlin-2 appears to play a functional role in prostate cancer cell sensitivity to cisplatin. Targeting Kindlin-2 may therefore improve drug efficacy and reduce drug doses, and would likely be beneficial for the treatment of prostate cancer.

Keywords: Kindlin-2, Cisplatin, Prostate cancer, Cell death