癌细胞显示的信号通路通常由与生理成分相同的成分组成,然而,总体结果是病理性失调。非受体蛋白酪氨酸激酶Src是一个很好的例子。Src是第一个被描述的原癌基因,也是癌症进展中被证明的参与者,因为它会影响扩散,入侵,生存,癌症干性,和抗药性。Src激活与许多癌症类型的不良预后有关,然而,这种蛋白质的突变很少被观察到。此外,作为一个被证明的癌症目标,已经证明激酶活性的非特异性抑制在临床中是无效的,因为在非癌细胞中抑制Src导致不可接受的毒性。因此,在Src中需要新的靶区域,只能在某些细胞类型中抑制Src活性,例如,癌细胞,同时维持健康细胞的正常生理活动。SrcN-末端调控元件(SNRE)包括对Src家族的每个成员具有独特序列的、研究较少的固有无序区域。从这个角度来看,我们讨论了涉及SNRE的非规范调节机制及其作为oncotargets的潜在用途。
The signaling pathways displayed by cancer cells are often composed by the same components than the physiological ones, yet the overall result is a pathological deregulation. The non-receptor protein tyrosine kinase Src is a good example. Src is the first described proto-oncogene and a demonstrated player in cancer progression, as it affects proliferation, invasion, survival, cancer stemness, and drug resistance. Src activation is linked to poor prognosis in many cancer types, yet mutations in this protein are rarely observed. In addition, being a demonstrated cancer target, unspecific inhibition of the kinase activity has proven inefficient in clinics since the inhibition of Src in non-cancerous cells results in unacceptable toxicity. Thus, there is a need for new target regions in Src that could inhibit Src activity only in certain cell types, e.g., cancer cells, while maintaining the normal physiological activity in healthy cells. The Src N-terminal regulatory element (SNRE) includes the poorly studied intrinsically disordered region with unique sequences for each of the members of the Src family. In this perspective, we discuss the non-canonical regulatory mechanisms involving the SNRE and their potential use as oncotargets.