MUC1 Promotes Cervical Squamous Cell Carcinoma Through ERK Phosphorylation-mediated Regulation of ITGA2/ITGA3

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2024 May 3

PMID 38702644

Authors

Aiqin Zhao

Yunzhi Pan

Yingyin Gao

Zheng Zhi

Haiying Lu

Bei Dong

Xuan Zhang

Meiying Wu

Fenxia Zhu

Sufang Zhou

Sai Ma

Affiliations

Soon will be listed here.

Abstract

In contrast to the decreasing trends in developed countries, the incidence and mortality rates of cervical squamous cell carcinoma in China have increased significantly. The screening and identification of reliable biomarkers and candidate drug targets for cervical squamous cell carcinoma are urgently needed to improve the survival rate and quality of life of patients. In this study, we demonstrated that the expression of MUC1 was greater in neoplastic tissues than in non-neoplastic tissues of the cervix, and cervical squamous cell carcinoma patients with high MUC1 expression had significantly worse overall survival than did those with low MUC1 expression, indicating its potential for early diagnosis of cervical squamous cell carcinoma. Next, we explored the regulatory mechanism of MUC1 in cervical squamous cell carcinoma. MUC1 could upregulate ITGA2 and ITGA3 expression via ERK phosphorylation, promoting the proliferation and metastasis of cervical cancer cells. Further knockdown of ITGA2 and ITGA3 significantly inhibited the tumorigenesis of cervical cancer cells. Moreover, we designed a combination drug regimen comprising MUC1-siRNA and a novel ERK inhibitor in vivo and found that the combination of these drugs achieved better results in animals with xenografts than did MUC1 alone. Overall, we discovered a novel regulatory pathway, MUC1/ERK/ITGA, in cervical squamous cell carcinoma that may serve as a potential biomarker and therapeutic target in the future.

Citing Articles

RPL22L1 fosters malignant features of cervical cancer via the modulation of DUSP6-ERK axis.

Zhang D, Zhao M, Jiang P, Zhou Y, Yan X, Zhou C J Transl Med. 2025; 23(1):244.

PMID: 40022129 PMC: 11871735. DOI: 10.1186/s12967-025-06249-0.

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