Cancer is frequently coupled with the disturbance of key signaling pathways. Aberrant activation of the mitogen-activated protein kinase (MAPK) signaling cascade, occurring in over 85% of cancers, is mainly caused by the genetic alterations of its main components—oncogenes EGFR and RAS, and plays a crucial role in cell fate. The importance of EGFR and RAS proteins in a variety of tumors suggests that they would be good therapeutic targets, but at present, no effective targeted therapy against these two oncogenes has been proven. Here, we show that ribonuclease from Bacillus pumilus (binase) inhibits MAPK signaling through direct interaction with EGFR and RAS proteins. This effect contributes to the antitumor potential of binase along with its enzymatic activity. Multitargeticity of binase prevents the development of drug resistance, which is considered a major obstacle to effective anticancer treatment.

中文翻译：

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两种主要癌症生物标志物作为双酶抗肿瘤活性的分子靶标

癌症常常与关键信号通路的紊乱相关。丝裂原激活蛋白激酶 (MAPK) 信号级联的异常激活发生在超过 85% 的癌症中，主要是由其主要成分癌基因 EGFR 和 RAS 的遗传改变引起的，在细胞命运中发挥着至关重要的作用。 EGFR和RAS蛋白在多种肿瘤中的重要性表明它们将是良好的治疗靶点，但目前尚未证明针对这两种癌基因的有效靶向治疗。在这里，我们证明来自短小芽孢杆菌的核糖核酸酶（双酶）通过与 EGFR 和 RAS 蛋白直接相互作用来抑制 MAPK 信号传导。这种效应有助于双酶的抗肿瘤潜力及其酶活性。双酶的多靶点性可防止耐药性的产生，这被认为是有效抗癌治疗的主要障碍。