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.
GRB2相关结合蛋白1（GAB1）是首个被发现的GAB/DOS家族成员，属于含有pleckstrin同源（PH）结构域的蛋白家族。在接收多种刺激信号后，GAB1从细胞质转位至细胞膜并被多种激酶磷酸化。这一过程招募了包含SH2结构域的蛋白如SHP2、PI3K的p85亚基、CRK等，进而激活包括MAPK、PI3K/AKT和JNK在内的不同信号通路。GAB1缺失的胚胎在子宫内死亡，并表现出心脏、胎盘、肝脏、皮肤、四肢及膈肌细胞的发育异常。在癌症背景下已发现GAB1的致癌性突变，其表达水平在多种肿瘤中发生紊乱，患者体内GAB1水平升高通常预示多种癌症类型的不良预后。本综述重点探讨GAB1对细胞恶性转化的影响，特别是在增殖、凋亡逃逸、转移和血管生成这些癌症标志性过程中的作用。GAB1还调节肿瘤对抗癌治疗的耐药性/敏感性，使其成为未来抗癌策略中极具潜力的靶点。
肿瘤(癌症)患者之家