ERBB2
小结
ERBB2是致癌基因，编码蛋白是酪氨酸激酶受体（ERBB）家族的成员之一。ERBB2又被称作HER2。ERBB2是跨膜酪氨酸激酶受体，由胞外的结合结构域和胞内的激酶结构域构成，ERBB2可以与其他ERBB家族受体发生异源二聚化并激活下游信号通路，包括MAPK和PI3K/AKT /mTOR信号通路。ERBB2还可以同源二聚化并启动MAPK，SRC，PI3K和STAT信号通路。ERBB2介导的信号传导的激活最终导致细胞增殖，迁移和分化。 在一系列人类癌症中ERBB2通过基因扩增和过表达激活下游信号通路，包括乳腺癌，非小细胞肺癌，胃癌和子宫内膜肿瘤等。乳腺癌中的ERBB2基因扩增与较差的总体存活和肿瘤复发时间相关。扩增的ERBB2与ERBB3异二聚化以激活致癌信号传导并驱动乳腺癌中的肿瘤发生。在小叶乳腺癌，肺腺癌和胃癌等一系列肿瘤中检测到ERBB2的体细胞的突变，以及细胞外和激酶结构域中的复发性热点改变。
ERBB2 (also HER2) is a transmembrane receptor that is a member of the ERBB family of receptor tyrosine kinases, including EGFR, ERBB3, and ERBB4. ERBB2 does not directly bind its own ligand; instead, it potentiates the activity of other ligand-bound ERBB receptors by binding to them. ERBB2 can heterodimerize with any of the other EGFR family receptors initiating downstream signaling activation of several pathways including the MAPK and PI3K/AKT/mTOR signaling cascades . ERBB2 can also homodimerize and initiate MAPK, SRC, PI3K and STAT signaling. Activation of ERBB2-mediated signaling ultimately results in cellular proliferation, migration, and differentiation . ERBB2 is activated by gene amplification and overexpression in a range of human cancers including breast, gastric, and endometrial tumors, among others. ERBB2 gene amplification in human breast cancers is associated with poor overall survival and time to tumor recurrence. Amplified ERBB2 heterodimerizes with ERBB3 to activate oncogenic signaling and drives tumorigenesis in breast cancer . Somatic mutations in ERBB2 have been identified in a series of tumors including lobular breast, lung adenocarcinoma, and gastric cancers, among others, with recurrent hotspot alterations in both the extracellular and kinase domains.