Crosstalk between RON and androgen receptor signaling in the development of castration resistant prostate cancer
| Autor: | Suleman S. Hussain, Peng Meng, Pawel A. Osmulski, Addanki P. Kumar, Tim H M Huang, Roble Bedolla, Huiyoung Yun, Amanda L. Profit, Izhar Singh Batth, Robert L. Reddick |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Gerontology Oncology medicine.medical_specialty FLIP medicine.drug_class Castrate-resistant prostate cancer urologic and male genital diseases 03 medical and health sciences Prostate cancer 0302 clinical medicine DU145 MST1R Internal medicine LNCaP Biomarkers Tumor Tumor Cells Cultured medicine Humans Epithelial–mesenchymal transition Cell Proliferation business.industry apoptosis Receptor Protein-Tyrosine Kinases Prognosis RON Androgen medicine.disease 3. Good health Androgen receptor Prostatic Neoplasms Castration-Resistant 030104 developmental biology Receptors Androgen 030220 oncology & carcinogenesis castrate resistant prostate cancer business Signal Transduction Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.7287 |
| Popis: | // Izhar Batth 1, 8 , Huiyoung Yun 2 , Suleman Hussain 2 , Peng Meng 1, 7 , Pawel Osmulski 3 , Tim Hui-Ming Huang 3, 5 , Roble Bedolla 1 , Amanda Profit 4 , Robert Reddick 4 , Addanki Kumar 1, 2, 3, 5, 6 1 Department of Urology, The University of Texas Health Science Center, San Antonio, TX, USA 2 Department of Pharmacology, The University of Texas Health Science Center, San Antonio, TX, USA 3 Department of Molecular Medicine, The University of Texas Health Science Center, San Antonio, TX, USA 4 Department of Pathology, The University of Texas Health Science Center, San Antonio, TX, USA 5 Cancer Therapy and Research Center, The University of Texas Health Science Center, San Antonio, TX, USA 6 The University of Texas Health Science Center at San Antonio and South Texas Veterans Health Care System, San Antonio, TX, USA 7 Current address: Life Sciences Division, Lawrence Berkley National Laboratory, Berkley, CA, USA 8 Current address: Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Correspondence to: Addanki Kumar, e-mail: kumara3@uthscsa.edu Keywords: castrate resistant prostate cancer, apoptosis, FLIP, RON, MST1R Received: November 18, 2015 Accepted: January 29, 2016 Published: February 9, 2016 ABSTRACT Castrate-resistant prostate cancer (CRPC) is the fatal form of prostate cancer. Although reactivation of androgen receptor (AR) occurs following androgen deprivation, the precise mechanism involved is unclear. Here we show that the receptor tyrosine kinase, RON alters mechanical properties of cells to influence epithelial to mesenchymal transition and functions as a transcription factor to differentially regulate AR signaling. RON inhibits AR activation and subset of AR-regulated transcripts in androgen responsive LNCaP cells. However in C4-2B, a castrate-resistant sub-line of LNCaP and AR-negative androgen independent DU145 cells, RON activates subset of AR-regulated transcripts. Expression of AR in PC-3 cells leads to activation of RON under androgen deprivation but not under androgen proficient conditions implicating a role for RON in androgen independence. Consistently, RON expression is significantly elevated in castrate resistant prostate tumors. Taken together our results suggest that RON activation could aid in promoting androgen independence and that inhibition of RON in combination with AR antagonist(s) merits serious consideration as a therapeutic option during hormone deprivation therapy. |
| Databáze: | OpenAIRE |
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