DNA Replication Licensing Protein MCM10 Promotes Tumor Progression and Is a Novel Prognostic Biomarker and Potential Therapeutic Target in Breast Cancer

Cancers

Youzhi Zhu¹  Yuchen Bai²  Ravikiran Mahadevappa²  ShunMing Yuen²  Muhammad Jameel²  HangFai Kwok²  Henrique Neves²  Hiu-Fung Yuen³  Shu-Dong Zhang⁴  Yao Lin⁵ 

[1] Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China;Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau, China;Institute of Molecular and Cell Biology, A*STAR, Singapore 138673, Singapore;Northern Ireland Centre for Stratified Medicine, Biomedical Sciences Research Institute, Ulster University, Londonderry BT47 6SB, UK;Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China;

关键词: MCM10;    breast cancer;    knockdown;    overexpression;    proliferation;    survival;   

DOI  :  10.3390/cancers10090282

来源: DOAJ

【 摘 要 】

Breast cancer is one of the most common malignancies in women worldwide. In breast cancer, the cell proliferation rate is known to influence the cancer malignancy. Recent studies have shown that DNA replication initiation/licensing factors are involved in cancer cell proliferation as well as cancer cell migration and invasion. Licensing factors have also been reported as important prognostic markers in lung, prostrate, and bladder cancers. Here, we studied the role of MCM10, a novel licensing factor, in breast cancer progression. From the public database, NCBI, we investigated six independent breast cancer patient cohorts, totaling 1283 patients. We observed a significant association between high MCM10 mRNA expression with tumor grading and patients’ survival time. Most importantly, using breast cancer cohorts with available treatment information, we also demonstrated that a high level of MCM10 is associated with a better response to conventional treatment. Similarly, in in vitro studies, the expression level of MCM10 in breast cancer cell lines is significantly higher compared to paired normal breast epithelium cells. Knockdown of MCM10 expression in the cancer cell line showed significantly decreased tumorigenic properties such as cell proliferation, migration and anchorage independence. The MCF7 breast cancer cell line, after MCM10 expression knockdown, showed significantly decreased tumorigenic properties such as cell proliferation, migration, and anchorage independent growth. Mechanistically, MCM10 expression is observed to be regulated by an Estrogen Receptor (ER) signaling pathway, where its expression is suppressed by the inhibition of the ER or serum withdrawal. Our results suggest that MCM10 plays an important role in breast cancer progression and is a potential prognostic/predictive biomarker and therapeutic target for breast cancer patients.

【 授权许可】

Unknown