Kindlin-2 controls sensitivity of prostate cancer cells to cisplatin-induced cell death.
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.
Gong
Xiaowei
X
Karolinska Institutet, Center for Biosciences, Department of Biosciences and Nutrition, SE-141 83 Huddinge, Sweden.
An
Zhengwen
Z
Wang
Yunling
Y
Guan
Lizhao
L
Fang
Weigang
W
Strömblad
Staffan
S
Jiang
Yong
Y
Zhang
Hongquan
H
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000502:physiology*; D009363:Neoplasm Proteins / Q000032:analysis / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D034622:RNA Interference
D000970:Antineoplastic Agents; C477322:FERMT3 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D002945:Cisplatin