One rapidly evolving area of research in my laboratory relates to identifying a new family of human tumor suppressors. While mutations in RAS genes are common in many cancers, RAS mutations are conspicuously rare in breast, prostate and brain tumors, suggesting that Ras is activated via alternative mechanisms. We have recently identified several members of the RasGAP gene family, that function as human tumor and metastasis suppressors. These RasGAPs normally function to turn off Ras, therefore their inactivation results in unrestricted Ras signaling. Moreover, we have found that these proteins often serve as signaling scaffolds, integrating Ras with other important signaling pathways, thus explaining their robust tumor and metastasis suppressing activity.
Publications
Abigail L. Miller, Naiara Perurena, Alycia Gardner, Toshinori Hinoue, Patrick Loi, Peter W. Laird, Karen Cichowski
Cancer Research, 2023 May 18
Loss of RasGAP Tumor Suppressors Underlies the Aggressive Nature of Luminal B Breast Cancers
Sarah Naomi Olsen, Ania Wronski, Zafira Castaño, Benjamin Dake, Clare Malone, Thomas De Raedt, Miriam Enos, Yoko S. DeRose, Wenhui Zhou, Stephanie Guerra, Massimo Loda, Alana Welm, Ann H. Partridge, Sandra S. McAllister, Charlotte Kuperwasser, Karen Cichowski
Cancer Discovery, vol. 7, 2017 Feb, pp. 202-217