The Role of GAB1 in Cancer

SIMPLE SUMMARY: GRB2-associated binder 1 (GAB1) is a docking protein pivotal in linking multiple stimuli to various intracellular signaling pathways. Embryonic development is disrupted in GAB1-deficient mice, and oncogenic mutations have been noted in cancer cases. In numerous types of cancer, high GAB1 expression levels correlate with a poor prognosis. Studies reveal that GAB1 significantly influences cellular transformation by changes in proliferation, evasion of apoptosis, metastasis, and angiogenesis—all fundamental processes in cancer development. Furthermore, GAB1 is implicated in the resistance/sensitivity to antitumor treatments, thus establishing its potential as an anticancer therapy target. ABSTRACT: GRB2-associated binder 1 (GAB1) is the inaugural member of the GAB/DOS family of pleckstrin homology (PH) domain-containing proteins. Upon receiving various stimuli, GAB1 transitions from the cytoplasm to the membrane where it is phosphorylated by a range of kinases. This event recruits SH2 domain-containing proteins like SHP2, PI3K’s p85 subunit, CRK, and others, thereby activating distinct signaling pathways, including MAPK, PI3K/AKT, and JNK. GAB1-deficient embryos succumb in utero, presenting with developmental abnormalities in the heart, placenta, liver, skin, limb, and diaphragm myocytes. Oncogenic mutations have been identified in the context of cancer. GAB1 expression levels are disrupted in various tumors, and elevated levels in patients often portend a worse prognosis in multiple cancer types. This review focuses on GAB1’s influence on cellular transformation particularly in proliferation, evasion of apoptosis, metastasis, and angiogenesis—each of these processes being a cancer hallmark. GAB1 also modulates the resistance/sensitivity to antitumor therapies, making it a promising target for future anticancer strategies.