Full Text | PDF

Share on tweeters Share on facebook Share on linkedin Share on googleplus

Int J Biol Sci 2021; 17(7):1671-1681. doi:10.7150/ijbs.57964 This issue Cite

Research Paper

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

Yuan Luo1*, Shijing Ma1,2*, Yingming Sun1*, Shan Peng1, Zihang Zeng1, Linzhi Han1, Shuying Li1, Wenjie Sun1, Jieyu Xu1, Xiaoli Tian1, Feng Wang1, Qiuji Wu1, Yu Xiao3, Junhong Zhang1,4,5, Yan Gong3✉, Conghua Xie1,4,5✉

1. Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.
2. Department of Geriatrics, Renmin Hospital of Wuhan University, Wuhan, China.
3. Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China.
4. Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, China.
5. Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
* These authors contributed equally to this work.

✉ Corresponding authors: Dr. Conghua Xie, Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, Hubei 430071, China, Phone: +86-27-67812607, Email: chxie_65edu.cn; and Dr. Yan Gong, Departmen More

Citation:
Luo Y, Ma S, Sun Y, Peng S, Zeng Z, Han L, Li S, Sun W, Xu J, Tian X, Wang F, Wu Q, Xiao Y, Zhang J, Gong Y, Xie C. MUC3A induces PD-L1 and reduces tyrosine kinase inhibitors effects in EGFR-mutant non-small cell lung cancer. Int J Biol Sci 2021; 17(7):1671-1681. doi:10.7150/ijbs.57964. https://www.ijbs.com/v17p1671.htm
Other styles

File import instruction

Abstract

Graphic abstract

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.

Keywords: MUC3A, non-small cell lung cancer, EGFR, PD-L1.

Citation styles

APA
Luo, Y., Ma, S., Sun, Y., Peng, S., Zeng, Z., Han, L., Li, S., Sun, W., Xu, J., Tian, X., Wang, F., Wu, Q., Xiao, Y., Zhang, J., Gong, Y., Xie, C. (2021). MUC3A induces PD-L1 and reduces tyrosine kinase inhibitors effects in EGFR-mutant non-small cell lung cancer. International Journal of Biological Sciences, 17(7), 1671-1681. https://doi.org/10.7150/ijbs.57964.

ACS
Luo, Y.; Ma, S.; Sun, Y.; Peng, S.; Zeng, Z.; Han, L.; Li, S.; Sun, W.; Xu, J.; Tian, X.; Wang, F.; Wu, Q.; Xiao, Y.; Zhang, J.; Gong, Y.; Xie, C. MUC3A induces PD-L1 and reduces tyrosine kinase inhibitors effects in EGFR-mutant non-small cell lung cancer. Int. J. Biol. Sci. 2021, 17 (7), 1671-1681. DOI: 10.7150/ijbs.57964.

NLM
Luo Y, Ma S, Sun Y, Peng S, Zeng Z, Han L, Li S, Sun W, Xu J, Tian X, Wang F, Wu Q, Xiao Y, Zhang J, Gong Y, Xie C. MUC3A induces PD-L1 and reduces tyrosine kinase inhibitors effects in EGFR-mutant non-small cell lung cancer. Int J Biol Sci 2021; 17(7):1671-1681. doi:10.7150/ijbs.57964. https://www.ijbs.com/v17p1671.htm

CSE
Luo Y, Ma S, Sun Y, Peng S, Zeng Z, Han L, Li S, Sun W, Xu J, Tian X, Wang F, Wu Q, Xiao Y, Zhang J, Gong Y, Xie C. 2021. MUC3A induces PD-L1 and reduces tyrosine kinase inhibitors effects in EGFR-mutant non-small cell lung cancer. Int J Biol Sci. 17(7):1671-1681.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

©2023 Ivyspring International Publisher. Terms of use