title: The RasGAP gene, RASAL2, is a tumor and metastasis suppressor.
abstract: RAS genes are commonly mutated in cancer; however, RAS mutations are rare in breast cancer, despite frequent hyperactivation of Ras and ERK. Here, we report that the RasGAP gene, RASAL2, functions as a tumor and metastasis suppressor. RASAL2 is mutated or suppressed in human breast cancer, and RASAL2 ablation promotes tumor growth, progression, and metastasis in mouse models. In human breast cancer, RASAL2 loss is associated with metastatic disease; low RASAL2 levels correlate with recurrence of luminal B tumors; and RASAL2 ablation promotes metastasis of luminal mouse tumors. Additional data reveal a broader role for RASAL2 inactivation in other tumor types. These studies highlight the expanding role of RasGAPs and reveal an alternative mechanism of activating Ras in cancer.
authors.affiliation: Genetics Division, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Sara Koenig
authors.initials: SK
authors.lastname: McLaughlin
authors.forename: Sarah Naomi
authors.initials: SN
authors.lastname: Olsen
authors.forename: Benjamin
authors.initials: B
authors.lastname: Dake
authors.forename: Thomas
authors.initials: T
authors.lastname: De Raedt
authors.forename: Elgene
authors.initials: E
authors.lastname: Lim
authors.forename: Roderick Terry
authors.initials: RT
authors.lastname: Bronson
authors.forename: Rameen
authors.initials: R
authors.lastname: Beroukhim
authors.forename: Kornelia
authors.initials: K
authors.lastname: Polyak
authors.forename: Myles
authors.initials: M
authors.lastname: Brown
authors.forename: Charlotte
authors.initials: C
authors.lastname: Kuperwasser
authors.forename: Karen
authors.initials: K
authors.lastname: Cichowski
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D020690:GTPase-Activating Proteins; D016158:Genes, p53; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D014183:Transplantation, Heterologous; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; C576391:RASAL2 protein, human; D025521:Tumor Suppressor Proteins; D020703:ras GTPase-Activating Proteins; D016283:Proto-Oncogene Proteins p21(ras)
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