1. RAL GTPases are linchpin modulators of human tumour‐cell proliferation and survival
- Author
-
Michael A. White and Yuchen Chien
- Subjects
Cell division ,Cell Survival ,Scientific Report ,Cell ,GTPase ,Biology ,Biochemistry ,RNA interference ,Cell Line, Tumor ,In Situ Nick-End Labeling ,Genetics ,medicine ,Humans ,Molecular Biology ,Cell Line, Transformed ,RALB ,Cell growth ,RALA ,Cell biology ,Cell Transformation, Neoplastic ,medicine.anatomical_structure ,Ral GTP-Binding Proteins ,RNA Interference ,ral GTP-Binding Proteins ,Cell Division ,HeLa Cells - Abstract
The monomeric RAL (RAS-like) GTPases have been indirectly implicated in mitogenic regulation and cell transformation. Here, we show that RALA and RALB collaborate to maintain tumorigenicity through regulation of both proliferation and survival. Remarkably, this task is divided between these highly homologous isoforms. RALB is specifically required for survival of tumour cells but not normal cells. RALA is dispensable for survival, but is required for anchorage-independent proliferation. Reducing the 'oncogenic burden' in human tumour cells relieves the sensitivity to loss of RALB. These observations establish RAL GTPases as crucial components of the cellular machinery that are exploited by factors that drive oncogenic transformation.
- Published
- 2003