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DNA replication licensing protein MCM10 promotes tumor progression and is a novel prognostic biomarker and potential therapeutic target in breast cancer
Mahadevappa R.1; Neves H.1; Yuen S.M.1; Jameel M.1; Bai Y.1; Yuen H.-F.2; Zhang S.-D.5; Zhu Y.4; Lin Y.3; Kwok H.F.1
2018-09-01
Source PublicationCancers
ISSN20726694
Volume10Issue:9
Abstract

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.

KeywordBreast Cancer Knockdown Mcm10 Overexpression Proliferation Survival
DOI10.3390/cancers10090282
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaOncology
WOS SubjectOncology
WOS IDWOS:000448139800006
Scopus ID2-s2.0-85052512180
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Citation statistics
Document TypeJournal article
CollectionBiological Imaging and Stem Cell Core
Faculty of Health Sciences
Cancer Centre
Animal Research Core
Corresponding AuthorKwok H.F.
Affiliation1.Universidade de Macau
2.A-Star, Institute of Molecular and Cell Biology
3.Fujian Normal University
4.Fujian Medical University
5.Ulster University
First Author AffilicationUniversity of Macau
Corresponding Author AffilicationUniversity of Macau
Recommended Citation
GB/T 7714
Mahadevappa R.,Neves H.,Yuen S.M.,et al. DNA replication licensing protein MCM10 promotes tumor progression and is a novel prognostic biomarker and potential therapeutic target in breast cancer[J]. Cancers, 2018, 10(9).
APA Mahadevappa R.., Neves H.., Yuen S.M.., Jameel M.., Bai Y.., Yuen H.-F.., Zhang S.-D.., Zhu Y.., Lin Y.., & Kwok H.F. (2018). DNA replication licensing protein MCM10 promotes tumor progression and is a novel prognostic biomarker and potential therapeutic target in breast cancer. Cancers, 10(9).
MLA Mahadevappa R.,et al."DNA replication licensing protein MCM10 promotes tumor progression and is a novel prognostic biomarker and potential therapeutic target in breast cancer".Cancers 10.9(2018).
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