FOXA1 is a determinant of drug resistance in breast cancer cells

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.

Prognostic Value of HER2-Low Expression in Non-Metastatic Triple-Negative Breast Cancer and Correlation with Other Biomarkers

“…While an association between the molecular apocrine subtype and HER2 overexpression (3+) has been previously reported [ 26 ], our results suggest that molecular apocrine tumors are more frequently HER2-low than HER2 0 cancers. This association, and the recent description of FOXA1 as a determinant of chemotherapy resistance in breast cancer cells [ 27 ], strengthen the rationale of trials to evaluate the combination of androgen receptor-targeting agents with new-generation anti-HER2 targeted therapies.…”

Characterization by Quantitative Serum Proteomics of Immune-Related Prognostic Biomarkers for COVID-19 Symptomatology

“…The FOXA1 transcription factor network (HNF3A pathway M285) BP with overrepresented proteins in response to COVID-19 increased in enrichment with disease severity (Figure 7). This pathway (https://www.gsea-msigdb.org/gsea/msigdb/cards/PID_ HNF3A_PATHWAY) coordinates function of primary airway epithelial cells (63) and has been associated with more aggressive breast (64) and prostate cancer (65). Accordingly, considering disorders and processes associated with COVID-19, these proteins may be proposed as candidate prognosis biomarkers for disease progression and severity (Figure 7).…”

Understanding the Role of Estrogen Receptor Status in PRODH/POX-Dependent Apoptosis/Survival in Breast Cancer Cells

“…The molecule required for the binding of ER to DNA is FoxA1. It is a critical factor that promotes binding to chromatin [ 6 ].…”

“…The molecule required for the binding of ER to DNA is FoxA1. It is a critical factor that promotes binding to chromatin [6]. Non-active ERs occur in the cell cytosol, where they form large complexes with chaperone proteins of the HSP (Heat Shock Proteins) family.…”

“…The molecule required for the binding of ER to DNA is FoxA1. It is a cr factor that promotes binding to chromatin [6]. The distribution of ERα and ERβ receptors in tissues and organs varies.…”