MUC3A induces PD-L1 and reduces tyrosine kinase inhibitors effects in EGFR-mutant non-small cell lung cancer.

Autor:	Luo Y; Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China., Ma S; Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.; Department of Geriatrics, Renmin Hospital of Wuhan University, Wuhan, China., Sun Y; Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China., Peng S; Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China., Zeng Z; Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China., Han L; Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China., Li S; Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China., Sun W; Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China., Xu J; Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China., Tian X; Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China., Wang F; Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China., Wu Q; Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China., Xiao Y; Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China., Zhang J; Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.; Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, China.; Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China., Gong Y; Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China., Xie C; Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.; Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, China.; Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
Jazyk:	angličtina
Zdroj:	International journal of biological sciences [Int J Biol Sci] 2021 Apr 12; Vol. 17 (7), pp. 1671-1681. Date of Electronic Publication: 2021 Apr 12 (Print Publication: 2021).
DOI:	10.7150/ijbs.57964
Abstrakt:	The immune checkpoint ligand programmed death-ligand 1 (PD-L1) and the transmembrane mucin (MUC) 3A are upregulated in non-small cell lung cancer (NSCLC), contributing to the aggressive pathogenesis and poor prognosis. Here, we report that knocking down the oncogenic MUC3A suppresses the PD-L1 expression in NSCLC cells. MUC3A is a potent regulator of epidermal growth factor receptor (EGFR) stability, and MUC3A deficiency downregulates the activation of the PI3K/Akt and MAPK pathways, which subsequently reduces the expression of PD-L1. Furthermore, knockdown of MUC3A and tyrosine kinase inhibitors (TKIs) in EGFR-mutant NSCLC cells play a synergistic effect on inhibited proliferation and promoted apoptosis in vitro . In the BALB/c nude mice xenograft model, MUC3A deficiency enhances EGFR-mutated NSCLC sensitivity to TKIs. Our study shows that transmembrane mucin MUC3A induces PD-L1, thereby promoting immune escape in NSCLC, while downregulation of MUC3A enhances TKIs effects in EGFR-mutant NSCLC. These findings offer insights into the design of novel combination treatment for NSCLC. Competing Interests: Competing Interests: The authors have declared that no competing interest exists. (© The author(s).)
Databáze:	MEDLINE
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