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

Ravikiran Mahadevappa, Henrique Neves, Shun Ming Yuen, Muhammad Jameel, Yuchen Bai, Hiu‑Fung Yuen, Shu-Dong Zhang, Youzhi Zhu, Yao Lin, Hang Fai Kwok

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.
LanguageEnglish
Article number282
Number of pages19
JournalCancers
Volume10
Issue number9
DOIs
Publication statusPublished - 22 Aug 2018

Fingerprint

Licensure
DNA Replication
Biomarkers
Breast Neoplasms
Neoplasms
Proteins
Cell Proliferation
Cell Movement
Therapeutics
Cell Line
Estrogen Receptors
Peptide Initiation Factors
Neoplasm Grading
Urinary Bladder Neoplasms
Lung Neoplasms
Breast
Epithelium
Databases
Messenger RNA
Survival

Keywords

  • MCM10
  • breast cancer
  • knockdown
  • overexpression
  • proliferation
  • survival

Cite this

Mahadevappa, Ravikiran ; Neves, Henrique ; Yuen, Shun Ming ; Jameel, Muhammad ; Bai, Yuchen ; Yuen, Hiu‑Fung ; Zhang, Shu-Dong ; Zhu, Youzhi ; Lin, Yao ; Kwok, Hang Fai. / DNA Replication Licensing Protein MCM10 Promotes Tumor Progression and Is a Novel Prognostic Biomarker and Potential Therapeutic Target in Breast Cancer. In: Cancers. 2018 ; Vol. 10, No. 9.
@article{979c2addf51f482b903d32a699a0f198,
title = "DNA Replication Licensing Protein MCM10 Promotes Tumor Progression and Is a Novel Prognostic Biomarker and Potential Therapeutic Target in Breast Cancer",
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.",
keywords = "MCM10, breast cancer, knockdown, overexpression, proliferation, survival",
author = "Ravikiran Mahadevappa and Henrique Neves and Yuen, {Shun Ming} and Muhammad Jameel and Yuchen Bai and Hiu‑Fung Yuen and Shu-Dong Zhang and Youzhi Zhu and Yao Lin and Kwok, {Hang Fai}",
year = "2018",
month = "8",
day = "22",
doi = "10.3390/cancers10090282",
language = "English",
volume = "10",
journal = "Cancers",
issn = "2072-6694",
publisher = "MDPI",
number = "9",

}

DNA Replication Licensing Protein MCM10 Promotes Tumor Progression and Is a Novel Prognostic Biomarker and Potential Therapeutic Target in Breast Cancer. / Mahadevappa, Ravikiran; Neves, Henrique; Yuen, Shun Ming; Jameel, Muhammad; Bai, Yuchen; Yuen, Hiu‑Fung; Zhang, Shu-Dong; Zhu, Youzhi; Lin, Yao; Kwok, Hang Fai.

In: Cancers, Vol. 10, No. 9, 282, 22.08.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - DNA Replication Licensing Protein MCM10 Promotes Tumor Progression and Is a Novel Prognostic Biomarker and Potential Therapeutic Target in Breast Cancer

AU - Mahadevappa, Ravikiran

AU - Neves, Henrique

AU - Yuen, Shun Ming

AU - Jameel, Muhammad

AU - Bai, Yuchen

AU - Yuen, Hiu‑Fung

AU - Zhang, Shu-Dong

AU - Zhu, Youzhi

AU - Lin, Yao

AU - Kwok, Hang Fai

PY - 2018/8/22

Y1 - 2018/8/22

N2 - 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.

AB - 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.

KW - MCM10

KW - breast cancer

KW - knockdown

KW - overexpression

KW - proliferation

KW - survival

U2 - 10.3390/cancers10090282

DO - 10.3390/cancers10090282

M3 - Article

VL - 10

JO - Cancers

T2 - Cancers

JF - Cancers

SN - 2072-6694

IS - 9

M1 - 282

ER -