A Thirty-year quest for a role of R-Ras in cancer: from an oncogene to a multitasking GTPase

• Published in: Cancer letters 2017-09, Vol.403, p.59-65
• Main Authors: Liu, Wai Nam, Yan, Mingfei, Chan, Andrew M
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Axon guidance; Biomarkers, Tumor - genetics; Biomarkers, Tumor - history; Biomarkers, Tumor - metabolism; Biomedical Research - history; Biomedical Research - methods; Breast cancer; Cancer; Cell adhesion; Cell adhesion & migration; Cell Adhesion Molecules - metabolism; Cell Communication; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cell Transformation, Neoplastic - pathology; Cloning; Deoxyribonucleic acid; DNA; Enzyme Activation; Gene expression; Genetic Predisposition to Disease; GTPase; Guanosine triphosphatases; Guanosine triphosphate; Hematology, Oncology and Palliative Medicine; History, 20th Century; History, 21st Century; Humans; Integrins; Kinases; Multitasking; Mutation; Neoplasms - enzymology; Neoplasms - genetics; Neoplasms - history; Neoplasms - pathology; Nerve Tissue Proteins - metabolism; Notch protein; Oncogene; Oncogenes; Phenotype; Prostate; Proteins; R-Ras; Ras; Ras protein; ras Proteins - genetics; ras Proteins - history; ras Proteins - metabolism; Semaphorins - metabolism; Signal Transduction; Tumorigenesis; Zebrafish
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2017.06.003

Abstract Since the identification of R-Ras, which is the first Ras-related GTPase isolated based on sequence similarity to the classical RAS oncogene, more than 160 members of the Ras superfamily of GTPases have been identified and classified into the Ras, Rho, Rap, Rab, Ran, Arf, Rheb, RGK, Rad, Rit, and Miro subfamilies. R-Ras belongs to the Ras subfamily of small G-proteins, which are frequently implicated in cell growth and differentiation. Although the roles of R-Ras in cellular transformation and integrin-mediated cell adhesion have been extensively studied, the physiological function of this enigmatic G-protein was only revealed when a mouse strain deficient in R-Ras was generated. In parallel, a plethora of research findings also linked R-Ras with processes including tumor angiogenesis, axon guidance, and immune cell trafficking. Several upstream factors that modulate R-Ras GTP-binding were identified including Notch, semaphorin, and chemokine C-C motif ligand 21. A review of our evolving understanding of the role of R-Ras in oncogenesis is timely, as this year marks the 30th anniversary of the publication describing the cloning of R-Ras.