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FOXA1 is a determinant of drug resistance in breast cancer cells

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Title: FOXA1 is a determinant of drug resistance in breast cancer cells
Authors: Kumar, U
Ardasheva, A
Mahmud, Z
Coombes, RC
Yague, E
Item Type: Journal Article
Abstract: Purpose Breast cancer is one of the most commonly diagnosed cancers in women. Five subtypes of breast cancer differ in their genetic expression profiles and carry different prognostic values, with no treatments available for some types, such as triple-negative, due to the absence of genetic signatures that could otherwise be targeted by molecular therapies. Although endocrine treatments are largely successful for estrogen receptor (ER)-positive cancers, a significant proportion of patients with metastatic tumors fail to respond and acquire resistance to therapy. FOXA1 overexpression mediates endocrine therapy resistance in ER-positive breast cancer, although the regulation of chemotherapy response by FOXA1 has not been addressed previously. FOXA1, together with EP300 and RUNX1, regulates the expression of E-cadherin, and is expressed in luminal, but absent in triple-negative and basal-like breast cancers. We have previously determined that EP300 regulates drug resistance and tumor initiation capabilities in breast cancer cells. Methods Here we describe the generation of breast cancer cell models in which FOXA1 expression has been modulated either by expression of hairpins targeting FOXA1 mRNA or overexpression plasmids. Results Upon FOXA1 knockdown in luminal MCF-7 and T47D cells, we found an increase in doxorubicin and paclitaxel sensitivity as well as a decrease in anchorage independence. Conversely, upregulation of FOXA1 in basal-like MDA-MB-231 cells led to an increase in drug resistance and anchorage independence. Conclusion Together, these data suggest that FOXA1 plays a role in making tumors more aggressive.
Issue Date: 8-Jan-2021
Date of Acceptance: 15-Dec-2020
URI: http://hdl.handle.net/10044/1/86299
DOI: 10.1007/s10549-020-06068-5
ISSN: 0167-6806
Publisher: Springer
Start Page: 317
End Page: 326
Journal / Book Title: Breast Cancer Research and Treatment
Volume: 186
Copyright Statement: © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
FOXA1
E-cadherin
Multidrug resistance
Breast cancer
Anchorage independence
EPITHELIAL-MESENCHYMAL TRANSITION
MESSENGER-RNA
EXPRESSION
CYTOTOXICITY
METASTASIS
ACTIVATION
MECHANISMS
PHENOTYPE
PATHWAYS
PROTEINS
Anchorage independence
Breast cancer
E-cadherin
FOXA1
Multidrug resistance
Science & Technology
Life Sciences & Biomedicine
Oncology
FOXA1
E-cadherin
Multidrug resistance
Breast cancer
Anchorage independence
EPITHELIAL-MESENCHYMAL TRANSITION
MESSENGER-RNA
EXPRESSION
CYTOTOXICITY
METASTASIS
ACTIVATION
MECHANISMS
PHENOTYPE
PATHWAYS
PROTEINS
Oncology & Carcinogenesis
1103 Clinical Sciences
1112 Oncology and Carcinogenesis
Publication Status: Published
Online Publication Date: 2021-01-08
Appears in Collections:Department of Surgery and Cancer
Faculty of Medicine



This item is licensed under a Creative Commons License Creative Commons