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Stem Cells International
Volume 2017, Article ID 5091541, 13 pages
https://doi.org/10.1155/2017/5091541
Research Article

Cadherins Associate with Distinct Stem Cell-Related Transcription Factors to Coordinate the Maintenance of Stemness in Triple-Negative Breast Cancer

1Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
2College of Pharmacy, Taishan Medical University, Tai’an, Shandong, China
3Department of Breast Surgery, Affiliated Hospital of Hebei University, Baoding, Hebei, China
4The Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA

Correspondence should be addressed to Yulong Liang; ude.mcb@gnoluy

Received 2 November 2016; Revised 5 January 2017; Accepted 17 January 2017; Published 14 March 2017

Academic Editor: Tong-Chuan He

Copyright © 2017 Chuanwei Yang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with poor prognosis and is enriched in cancer stem cells (CSCs). However, it is not completely understood how the CSCs were maintained in TNBC. In this study, by analyzing The Cancer Genome Atlas (TCGA) provisional datasets and several small-size breast datasets, we found that cadherins (CDHs) 2, 4, 6, and 17 were frequently amplified/overexpressed in 47% of TNBC while E-cadherin (CDH1) was downregulated/mutated at 10%. The alterations of CDH2/4/6/17 were strongly associated with the elevated levels of several stem cell-related transcription factors (SC-TFs) including FOXM1, MCM2, WWTR1, SNAI1, and SOX9. CDH2/4/6/17-enriched genes including FOXM1 and MCM2 were also clustered and regulated by NFY (nuclear transcription factor Y) and/or EVI1/MECOM. Meanwhile, these SC-TFs including NFYA were upregulated in TNBC cells, but they were downregulated in luminal type of cells. Furthermore, small compounds might be predicted via the Connectivity Map analysis to target TNBC with the alterations of CDH2/4/6/17 and SC-TFs. Together with the important role of these SC-TFs in the stem cell regulation, our data provide novel insights into the maintenance of CSCs in TNBC and the discovery of these SC-TFs associated with the alterations of CDH2/4/6/17 has an implication in targeted therapy of TNBC.