Yan Gao1, Yun-Sok Ha2, Tae Gyun Kwon2,3, Young-Chang Cho4, Sangkyu Lee5, Jun Nyung Lee6. 1. BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea. 2. Department of Urology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. 3. Joint Institute for Regenerative Medicine, Kyungpook National University, Daegu, Republic of Korea. 4. College of Pharmacy, Chonnam National University, Gwangju, Republic of Korea. 5. BK21 Plus KNU Multi-Omics Based Creative Drug Research Team, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea ljnlover@gmail.com sangkyu@knu.ac.kr. 6. Department of Urology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea ljnlover@gmail.com sangkyu@knu.ac.kr.
Abstract
BACKGROUND/AIM: Prostate cancer (PCa) is the second-most commonly occurring cancer among men, worldwide. Although the mechanisms associated with the progression of castration-resistant prostate cancer (CRPC) have been widely studied, the mechanism associated with more distant metastases from the bone remains unknown. This study aimed to characterize potential pathogenic kinases associated with highly metastatic PCa, that may regulate phosphorylation in extensively involved and diverse signaling pathways that are associated with the development of various cancers. MATERIALS AND METHODS: A mass spectrometry (MS)-based comparative phosphoproteome strategy was utilized to identify differentially expressed kinases between the highly aggressive PCa cell-lines PC-3 and PC-3M. RESULTS: Among 2,968 phosphorylation sites in PCa cells, 151 differently expressed phosphoproteins were identified. Seven motifs: -SP-, -SxxE-, -PxS-, -PxSP-, -SxxK-, -SPxK-, and -SxxxxxP- were found to be highly expressed in PC-3M cells. Based on these motifs, the kinases p21-activated kinase (PAK)2, Ste20-like kinase (SLK), mammalian Ste20-like kinase (MST)4, mitogen-activated kinase kinase (MAP2K)2, and A-Raf proto-oncogene serine/threonine kinase (ARAF) were up-regulated in PC-3M cells. CONCLUSION: PAK2, SLK, MST4, MAP2K2, and ARAF are kinases that are potentially associated with the progression of increased migration in PC-3M cells and may represent molecule regulators or drug targets for highly metastatic PCa therapy. Copyright
BACKGROUND/AIM: Prostate cancer (PCa) is the second-most commonly occurring cancer among men, worldwide. Although the mechanisms associated with the progression of castration-resistant prostate cancer (CRPC) have been widely studied, the mechanism associated with more distant metastases from the bone remains unknown. This study aimed to characterize potential pathogenic kinases associated with highly metastatic PCa, that may regulate phosphorylation in extensively involved and diverse signaling pathways that are associated with the development of various cancers. MATERIALS AND METHODS: A mass spectrometry (MS)-based comparative phosphoproteome strategy was utilized to identify differentially expressed kinases between the highly aggressive PCa cell-lines PC-3 and PC-3M. RESULTS: Among 2,968 phosphorylation sites in PCa cells, 151 differently expressed phosphoproteins were identified. Seven motifs: -SP-, -SxxE-, -PxS-, -PxSP-, -SxxK-, -SPxK-, and -SxxxxxP- were found to be highly expressed in PC-3M cells. Based on these motifs, the kinases p21-activated kinase (PAK)2, Ste20-like kinase (SLK), mammalianSte20-like kinase (MST)4, mitogen-activated kinase kinase (MAP2K)2, and A-Raf proto-oncogene serine/threonine kinase (ARAF) were up-regulated in PC-3M cells. CONCLUSION:PAK2, SLK, MST4, MAP2K2, and ARAF are kinases that are potentially associated with the progression of increased migration in PC-3M cells and may represent molecule regulators or drug targets for highly metastatic PCa therapy. Copyright
Authors: Varadha Balaji Venkadakrishnan; Adam D DePriest; Sangeeta Kumari; Dhirodatta Senapati; Salma Ben-Salem; Yixue Su; Giridhar Mudduluru; Qiang Hu; Eduardo Cortes; Elena Pop; James L Mohler; Gissou Azabdaftari; Kristopher Attwood; Rajal B Shah; Christina Jamieson; Scott M Dehm; Cristina Magi-Galluzzi; Eric Klein; Nima Sharifi; Song Liu; Hannelore V Heemers Journal: Oncogene Date: 2019-02-11 Impact factor: 9.867