
The R-RAS2 GTP hydrolase (GTPase) (also known as TC21) has been traditionally considered quite similar to classical RAS proteins at the regulatory and signalling levels. However, the present study reported that many RRAS2 mutations in human cancers are highly transforming when expressed in immortalized cell lines. Moreover, the expression of endogenous R-RAS2Q72L is essential for maintaining optimal levels of PI3K and ERK activities and for the adhesion, invasiveness, proliferation, and mitochondrial respiration of ovarian and breast cancer cell lines. These results indicated that gain-of-function mutations of R-RAS2/TC21 play roles in tumor initiation and maintenance that are not fully redundant with those regulated by classical RAS oncoproteins.
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