| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2108031 | Cancer Cell | 2014 | 15 Pages |
•Aberrantly overexpressed RBJ correlates to progression of human cancers•Nucleus-localized RBJ interacts with and entraps active MEK1/MEK2 in the nucleus•Rbj deficiency impairs AOM/DSS-induced carcinogenesis and tumor progression•Knockdown of Rbj inhibits tumor growth
SummaryRas-related small GTPases play important roles in cancer. However, the roles of RBJ, a representative of the sixth subfamily of Ras-related small GTPases, in tumorigenesis and tumor progression remain unknown. Here, we report that RBJ is dysregulated in human gastrointestinal cancers and can promote carcinogenesis and tumor progression via nuclear entrapment of mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)1/MEK2 and activation of ERK1/ERK2. Nucleus-localized RBJ interacts with MEK/ERK and prolongs the duration of MEK/ERK activation. Rbj deficiency abrogates nuclear accumulation of MEK1/MEK2, attenuates ERK1/ERK2 activation, and impairs AOM/DSS-induced colonic carcinogenesis. Moreover, Rbj knockdown inhibits growth of established tumors. Our data suggest that RBJ may be an oncogenic Ras-related small GTPase mediating nuclear accumulation of active MEK1/MEK2 in tumor progression.
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