Small GTPases of RAS act as centers of intracellular signal transduction and translate external stimuli to the various cellular responses. Embryonic stem cell expressed RAS (ERAS) is a member of the RAS family that is specifically expressed in undifferentiated mouse embryonic stem cells, hepatic stellate cells and several human tumors, such as gastric, breast, brain, pancreatic, and colorectal tumors. Although ERAS belongs to GTPase family, however it is not very efficient enzyme to hydrolyze GTP to GDP. Therefore, it remains mainly in its GTP-bound (active) form which results in sustained signal transduction. In comparison with classical RAS family members (HRAS, NRAS and KRAS4B), ERAS is known as a unique member, due to its temporal expression as well as remarkable sequence and functional differences. In this minireview, I compare in great details the biochemical properties of ERAS with conventional RAS family (HRAS, NRAS and KRAS4B). Recently, ERAS is introduced as a potential marker for drug resistance in several human tumors, therefore, I discuss main downstream signaling pathway of ERAS, PI3K-AKT-mTORC and its connection towards anti-apoptotic and cell-survival responses. By targeting this signaling axis, I hope to be able to sensitize ERAS expressing to chemotherapy.

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