CD73 在非小细胞肺癌中受 EGFR-ERK 信号通路调控。
CD73 Is Regulated by the EGFR-ERK Signaling Pathway in Non-small Cell Lung Cancer.
机构信息
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan, R.O.C.
National Taiwan University Cancer Center, College of Medicine, National Taiwan University, Taipei, Taiwan, R.O.C.
出版信息
Anticancer Res. 2021 Mar;41(3):1231-1242. doi: 10.21873/anticanres.14880.
BACKGROUND/AIM: Successful therapy of EGFR-mutant NSCLC remains a challenging task despite initial benefits with the usage of EGFR tyrosine kinase inhibitors. Cancer immunotherapy has shown promising results in certain tumors, but response rate in EGFR-mutant NCLC is low, because these tumors are thought to have weak immunogenicity.
MATERIALS AND METHODS
We used data from in vivo NSCLC databases as well as from in vitro cell culture experiments to investigate the regulation of CD73 by EGFR.
RESULTS
EGFR expression was correlated with CD73 expression in patients' datasets, with EGFR-mutant tumors showing higher expression than their EGFR wildtype counterparts. Treatment of EGFR-mutant NSCLC cell lines with EGFR TKI reduced expression of CD73 at both mRNA and protein level. Among EGFR downstream signaling pathways, the Ras-Raf-ERK pathway was involved in the regulation of CD73 expression directly via ERK1/2 without the engagement of RSKs or MSKs.
CONCLUSION
The results of this study may provide novel therapeutic strategies for the treatment of oncogene-driven NSCLC.
背景/目的：尽管表皮生长因子受体（EGFR）酪氨酸激酶抑制剂的应用最初带来了益处，但成功治疗 EGFR 突变型非小细胞肺癌（NSCLC）仍然是一项具有挑战性的任务。癌症免疫疗法在某些肿瘤中显示出了有前景的结果，但在 EGFR 突变型 NSCLC 中的反应率较低，因为这些肿瘤被认为具有较弱的免疫原性。
材料和方法
我们使用来自体内 NSCLC 数据库和体外细胞培养实验的数据来研究 EGFR 对 CD73 的调节作用。
结果
EGFR 表达与患者数据集的 CD73 表达相关，EGFR 突变型肿瘤的表达高于其 EGFR 野生型肿瘤。用 EGFR TKI 处理 EGFR 突变型 NSCLC 细胞系，可在 mRNA 和蛋白水平上降低 CD73 的表达。在 EGFR 下游信号通路中，Ras-Raf-ERK 通路通过 ERK1/2 直接参与 CD73 表达的调节，而无需 RSKs 或 MSKs 的参与。
结论
这项研究的结果可能为治疗驱动癌基因的 NSCLC 提供新的治疗策略。
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