表皮生长因子受体(EGFR)是第一个与人类癌症相关的酪氨酸激酶受体。EGFR或ERBB1是ERBB亚家族的成员,由四种I型跨膜受体酪氨酸激酶组成,ERBB1、2、3和4。除了ERBB2之外,ERBB在配体结合后形成同源/异源二聚体,并因此被激活。不同的信号通路,如磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT),RAS/RAF/MEK/ERK,磷脂酶Cγ和JAK-STAT,由ERBB激活触发。自从ERBB以来,通过这些途径,调节肿瘤干细胞(CSC)的干细胞和分化,它们在CSC致瘤性中的作用已被广泛研究。在许多类型的人类癌症中经常描述由遗传和/或表观遗传因素刺激的ERBBs及其下游途径的过度活化。它们的失调使细胞获得CSC特征,如存活,致瘤性和干性。由于在肿瘤生长和进展中的作用,ERBBs被认为是作为癌症治疗策略的药物靶标之一。在这一章中,我们将总结结构,ERBB亚家族的功能和作用及其调节CSCs干性和致瘤性的相关途径。最后,除了一些挑战和未来前景外,我们将讨论癌症的靶向治疗策略以及ERBBs。
The epidermal growth factor receptor (EGFR) was first tyrosine kinase receptor linked to human cancers. EGFR or ERBB1 is a member of ERBB subfamily, which consists of four type I transmembrane receptor tyrosine kinases, ERBB1, 2, 3 and 4.
ERBBs form homo/heterodimers after ligand binding except ERBB2 and consequently becomes activated. Different signal pathways, such as phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT), RAS/RAF/MEK/ERK, phospholipase Cγ and JAK-STAT, are triggered by ERBB activation. Since
ERBBs, through these pathways, regulate stemness and differentiation of cancer stem cells (CSCs), their roles in CSC tumorigenicity have extensively been investigated. The hyperactivation of
ERBBs and its downstream pathways stimulated by either genetic and/or epigenetic factors are frequently described in many types of human cancers. Their dysregulations make cells acquiring CSC characters such as survival, tumorigenicity and stemness. Because of the roles in tumor growth and progress,
ERBBs are considered to be one of the drug targets as cancer treatment strategy. In this chapter, we will summarize the structure, function and roles of ERBB subfamily along with their relative pathways regulating the stemness and tumorigenicity of CSCs. Finally, we will discuss the targeting therapy strategies of cancer along with
ERBBs in addition to some challenges and future perspectives.