Ma Yuhong, Zhang Feng, Li Jin, Li Juan, Li Yanhua
Department of Radiotherapy Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Department of International Medical Department, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Front Cell Dev Biol. 2024 Dec 24;12:1436033. doi: 10.3389/fcell.2024.1436033. eCollection 2024.
Non-small cell lung cancer (NSCLC) is the main histological subtype of lung cancer. For locally advanced and advanced NSCLC, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-targeted therapy has been the first choice for NSCLC patients with EGFR mutations. TKIs, as targeted drugs, inhibit kinase activity and autophosphorylation by competitively binding to the ATP binding site of the EGFR tyrosine kinase domain, which blocks the signal transduction mediated by EGFR and thus inhibits the proliferation of tumor cells. However, drug resistance to TKIs is inevitable. EGFR is also a highly glycosylated receptor tyrosine kinase, and a wide range of crosstalk occurs between phosphorylation and glycosylation. Therefore, can the phosphorylation state be altered by glycosylation to improve drug resistance? In this review, we summarize phosphorylation, glycosylation and the crosstalk between these processes as well as the current research status and methods. We also summarize the autophosphorylation and glycosylation sites of the EGFR protein and their crosstalk. By exploring the relationship between EGFR glycosylation and autophosphorylation in targeted TKI therapy, we find that research on EGFR glycosylation is crucial for targeted NSCLC treatment and will become a research direction for identifying potential targets related to regulating TKI drug sensitivity.
非小细胞肺癌（NSCLC）是肺癌的主要组织学亚型。对于局部晚期和晚期NSCLC，表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）靶向治疗一直是EGFR突变NSCLC患者的首选。TKI作为靶向药物，通过竞争性结合EGFR酪氨酸激酶结构域的ATP结合位点来抑制激酶活性和自磷酸化，从而阻断EGFR介导的信号转导，进而抑制肿瘤细胞的增殖。然而，对TKI产生耐药性是不可避免的。EGFR也是一种高度糖基化的受体酪氨酸激酶，磷酸化和糖基化之间存在广泛的相互作用。那么，糖基化能否改变磷酸化状态以提高耐药性呢？在这篇综述中，我们总结了磷酸化、糖基化以及这些过程之间的相互作用，以及当前的研究现状和方法。我们还总结了EGFR蛋白的自磷酸化和糖基化位点及其相互作用。通过探索靶向TKI治疗中EGFR糖基化与自磷酸化之间的关系，我们发现对EGFR糖基化的研究对于NSCLC靶向治疗至关重要，并将成为识别与调节TKI药物敏感性相关潜在靶点的研究方向。
