Exp Mol Med.
2014 Jul;46(7):e104. 10.1038/emm.2014.34.
Kruppel-like factor 4 mediates lysophosphatidic acid-stimulated migration and proliferation of PC3M prostate cancer cells
- Affiliations
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- 1Medical Research Center for Ischemic Tissue Regeneration, School of Medicine, Pusan National University, Yangsan, Republic of Korea. jhkimst@pusan.ac.kr
- 2Department of Physiology, School of Medicine, Pusan National University, Yangsan, Republic of Korea.
- 3Medical Research Institute, Pusan National University, Yangsan, Republic of Korea.
- 4Research Institute of Convergence Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea.
- KMID: 2155369
- DOI: http://doi.org/10.1038/emm.2014.34
Abstract
- Prostate cancer is the most frequently diagnosed malignancy and the second leading cause of cancer mortality among men in the United States. Accumulating evidence suggests that lysophosphatidic acid (LPA) serves as an autocrine/paracrine mediator to affect initiation, progression and metastasis of prostate cancer. In the current study, we demonstrate that LPA stimulates migration and proliferation of highly metastatic human prostate cancer, PC-3M-luc-C6 cells. LPA-induced migration of PC-3M-luc-C6 cells was abrogated by pretreatment of PC-3M-luc-C6 cells with the LPA receptor 1/3 inhibitor Ki16425 or small interfering RNA (siRNA)-mediated silencing of endogenous LPA receptor 1, implicating a key role of the LPA-LPA receptor 1 signaling axis in migration of PC-3M-luc-C6 cells. In addition, LPA treatment resulted in augmented expression levels of Kruppel-like factor 4 (KLF4), and siRNA or short-hairpin RNA (shRNA)-mediated silencing of KLF4 expression resulted in the abolishment of LPA-stimulated migration and proliferation of PC-3M-luc-C6 cells. shRNA-mediated silencing of KLF4 expression resulted in the inhibition of in vivo growth of PC-3M-luc-C6 cells in a xenograft transplantation animal model. Taken together, these results suggest a key role of LPA-induced KLF4 expression in cell migration and proliferation of prostate cancer cells in vitro and in vivo.
MeSH Terms
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Animals
Cell Line, Tumor
Cell Movement
Cell Proliferation
Gene Silencing
Humans
Kruppel-Like Transcription Factors/genetics/*metabolism
Lysophospholipids/*metabolism
Male
Mice, Inbred BALB C
Prostate/metabolism/*pathology
Prostatic Neoplasms/genetics/*metabolism/*pathology
Kruppel-Like Transcription Factors
Lysophospholipids
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