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YES1 在癌症中的新兴作用:耐药性的潜在靶点。

Emerging Roles of YES1 in Cancer: The Putative Target in Drug Resistance.

机构信息

Department of Chemistry, Kyonggi University, Suwon 16227, Republic of Korea.

College of Pharmacy, Keimyung University, Daegu 42691, Republic of Korea.

出版信息

Int J Mol Sci. 2024 Jan 25;25(3):1450. doi: 10.3390/ijms25031450.

Abstract

Src family kinases (SFKs) are non-receptor tyrosine kinases that are recognized as proto-oncogenic products. Among SFKs, YES1 is frequently amplified and overexpressed in a variety of human tumors, including lung, breast, ovarian, and skin cancers. YES1 plays a pivotal role in promoting cell proliferation, survival, and invasiveness during tumor development. Recent findings indicate that YES1 expression and activation are associated with resistance to chemotherapeutic drugs and tyrosine kinase inhibitors in human malignancies. YES1 undergoes post-translational modifications, such as lipidation and nitrosylation, which can modulate its catalytic activity, subcellular localization, and binding affinity for substrate proteins. Therefore, we investigated the diverse mechanisms governing YES1 activation and its impact on critical intracellular signal transduction pathways. We emphasized the function of YES1 as a potential mechanism contributing to the anticancer drug resistance emergence.

摘要

Src 家族激酶(SFKs)是非受体酪氨酸激酶,被认为是原癌基因产物。在 SFKs 中,YES1 在多种人类肿瘤中经常扩增和过表达,包括肺癌、乳腺癌、卵巢癌和皮肤癌。YES1 在肿瘤发展过程中在促进细胞增殖、存活和侵袭方面发挥着关键作用。最近的研究结果表明,YES1 的表达和激活与人类恶性肿瘤对化疗药物和酪氨酸激酶抑制剂的耐药性有关。YES1 经历翻译后修饰,如脂质化和硝化,这可以调节其催化活性、亚细胞定位和与底物蛋白的结合亲和力。因此,我们研究了调控 YES1 激活及其对关键细胞内信号转导途径影响的多种机制。我们强调了 YES1 作为一种潜在的机制在抗癌药物耐药性产生中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0158/10855972/caa7d7125e82/ijms-25-01450-g001.jpg

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