The RasGAP Gene, RASAL2, Is a Tumor and Metastasis Suppressor

被引：103

作者：

McLaughlin, Sara Koenig ^{[1
,2
,3
]}

Olsen, Sarah Naomi ^{[1
,2
,3
]}

Dake, Benjamin ^{[4
,5
]}

De Raedt, Thomas ^{[1
,2
,3
,10
]}

Lim, Elgene ^{[2
,3
,6
]}

Bronson, Roderick Terry ^{[3
]}

Beroukhim, Rameen ^{[2
,3
,7
,8
,9
]}

Polyak, Kornelia ^{[2
,3
,6
]}

Brown, Myles ^{[2
,3
,6
]}

Kuperwasser, Charlotte ^{[4
,5
]}

Cichowski, Karen ^{[1
,2
,3
,10
]}

机构：

[1] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA

[2] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Boston, MA 02115 USA

[4] Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Dept Dev Mol & Biochem Biol, Boston, MA 02111 USA

[5] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA

[6] Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02215 USA

[7] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA

[8] MIT, Broad Inst, Cambridge, MA 02142 USA

[9] Harvard Univ, Cambridge, MA 02142 USA

[10] Harvard Canc Ctr, Ludwig Ctr Dana Farber, Boston, MA 02115 USA

来源：

CANCER CELL | 2013年 / 24卷 / 03期

基金：

美国国家卫生研究院;

关键词：

ACTIVATED PROTEIN-KINASE; HUMAN BREAST; MOLECULAR PORTRAITS; SOMATIC MUTATIONS; EXPRESSION; NF1; ONCOGENES; PATHWAYS; PATTERNS; SURVIVAL;

D O I：

10.1016/j.ccr.2013.08.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 lumina! 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.

引用

页码：365 / 378

页数：14

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