RalBP1 is necessary for metastasis of human cancer cell lines

作者: Zhong Wu , Charles Owens , Nidhi Chandra , Kay Popovic , Mark Conaway

DOI: 10.1593/NEO.101080

关键词: Bone metastasisRal GTP-Binding ProteinsCancer researchBiologyCell growthCell migrationRALACancerMolecular biologyCancer cellMetastasis

摘要: RalA expression in human prostate cancer is associated with cell migration and necessary for bone metastasis. However, the downstream effectors of that mediate these functions remain unclear. Here we examined after small interfering RNA-mediated depletion Ral binding protein 1 (RalBP1/RLIP), exocyst complex component 2 (Sec5), phospholipase D1 (PLD1) found RalBP1 inhibited to a similar extent. Stable lentivirus short hairpin PC3 cells metastasis intracardiac inoculation. Depletion diminished orthotopic tumor growth spontaneous from this site. Interestingly, wild-type or mutants deficient was effective at rescuing reduced metastatic capacity RalA-depleted cells, suggesting does not reduce solely by interaction RalBP1. To determine whether role relevant beyond cancer, studied requirement an experimental model bladder type high expression. UMUC3 resulted decreased lung colonization while having minimal effect on subcutaneous growth. Our studies are first suggest Furthermore, show manifestation phenotype entirely dependent RalA-RalBP1 interaction.

参考文章(24)
Dan Theodorescu, John J. Gildea, Christopher A. Moskaluk, Michael A. Harding, Henry F. Frierson, Gary Oxford, Garret M. Hampton, M. Jabed Seraj, Mark R. Conaway, RhoGDI2 is an invasion and metastasis suppressor gene in human cancer. Cancer Research. ,vol. 62, pp. 6418- 6423 ,(2002)
Sooryanarayana Varambally, Jianjun Yu, Bharathi Laxman, Daniel R Rhodes, Rohit Mehra, Scott A Tomlins, Rajal B Shah, Uma Chandran, Federico A Monzon, Michael J Becich, John T Wei, Kenneth J Pienta, Debashis Ghosh, Mark A Rubin, Arul M Chinnaiyan, None, Integrative genomic and proteomic analysis of prostate cancer reveals signatures of metastatic progression. Cancer Cell. ,vol. 8, pp. 393- 406 ,(2005) , 10.1016/J.CCR.2005.10.001
Y Wu, K McRoberts, S S Berr, H F Frierson, M Conaway, D Theodorescu, Neuromedin U is regulated by the metastasis suppressor RhoGDI2 and is a novel promoter of tumor formation, lung metastasis and cancer cachexia. Oncogene. ,vol. 26, pp. 765- 773 ,(2007) , 10.1038/SJ.ONC.1209835
Yuchen Chien, Sungchan Kim, Ron Bumeister, Yueh-Ming Loo, Sung Won Kwon, Cynthia L Johnson, Mirey G Balakireva, Yves Romeo, Levy Kopelovich, Michael Gale, Charles Yeaman, Jacques H Camonis, Yingming Zhao, Michael A White, None, RalB GTPase-Mediated Activation of the IκB Family Kinase TBK1 Couples Innate Immune Signaling to Tumor Cell Survival Cell. ,vol. 127, pp. 157- 170 ,(2006) , 10.1016/J.CELL.2006.08.034
Brian E. Nicholson, Henry F. Frierson, Mark R. Conaway, Jabed M. Seraj, Michael A. Harding, Garret M. Hampton, Dan Theodorescu, Profiling the Evolution of Human Metastatic Bladder Cancer Cancer Research. ,vol. 64, pp. 7813- 7821 ,(2004) , 10.1158/0008-5472.CAN-04-0826
Kian-Huat Lim, Antonio T. Baines, James J. Fiordalisi, Michail Shipitsin, Larry A. Feig, Adrienne D. Cox, Channing J. Der, Christopher M. Counter, Activation of RalA is critical for Ras-induced tumorigenesis of human cells Cancer Cell. ,vol. 7, pp. 533- 545 ,(2005) , 10.1016/J.CCR.2005.04.030
Steven Christopher Smith, Gary Oxford, Alexander S. Baras, Charles Owens, Dmytro Havaleshko, David L. Brautigan, Martin K. Safo, Dan Theodorescu, Expression of ral GTPases, their effectors, and activators in human bladder cancer. Clinical Cancer Research. ,vol. 13, pp. 3803- 3813 ,(2007) , 10.1158/1078-0432.CCR-06-2419
Brian O. Bodemann, Michael A. White, Ral GTPases and cancer: linchpin support of the tumorigenic platform Nature Reviews Cancer. ,vol. 8, pp. 133- 140 ,(2008) , 10.1038/NRC2296
Sanjay Awasthi, Sharad S. Singhal, Yogesh C. Awasthi, Bryan Martin, Jung-Hee Woo, C. Casey Cunningham, Arthur E. Frankel, RLIP76 and Cancer Clinical Cancer Research. ,vol. 14, pp. 4372- 4377 ,(2008) , 10.1158/1078-0432.CCR-08-0145
Do Sik Min, Taeg Kyu Kwon, Won-Sang Park, Jong-Soo Chang, Seung-Kiel Park, Bong-Hyun Ahn, Zae-Young Ryoo, Young Han Lee, Yeon Soo Lee, Duck-Joo Rhie, Shin-Hee Yoon, Sang June Hahn, Myung-Suk Kim, Yang-Hyeok Jo, Neoplastic transformation and tumorigenesis associated with overexpression of phospholipase D isozymes in cultured murine fibroblasts. Carcinogenesis. ,vol. 22, pp. 1641- 1647 ,(2001) , 10.1093/CARCIN/22.10.1641