KLF4 defines the efficacy of the epidermal growth factor receptor inhibitor, erlotinib, in triple-negative breast cancer cells by repressing the EGFR gene
Abstract
Triple-negative breast cancer (TNBC) is characterized by high rates of recurrence and poor overall survival. This is due, in part, to a deficiency of targeted therapies, making it essential to identify therapeutically targetable driver pathways of this disease. While epidermal growth factor receptor (EGFR) is expressed in 60% of TNBCs and drives disease progression, attempts to inhibit EGFR in unselected TNBC patients have had a marginal impact on outcomes. Hence, we sought to identify the mechanisms that dictate EGFR expression and inhibitor response to provide a path for improving the utility of these drugs. In this regard, the majority of TNBCs express low levels of the transcription factor, Krüppel-like factor 4 (KLF4), while a small subset is associated with high expression. KLF4 and EGFR have also been reported to have opposing actions in TNBC. Thus, we tested whether KLF4 controls the expression of EGFR and cellular response to its pharmacological inhibition.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 18, 2020
- Source ID
- 10.1186/s13058-020-01305-7
Entities
People
- Benjamin L. Bryson
- Bryan M. Webb
- Darcie D. Seachrist
- Kristen L. Weber-bonk
- Lindsey J. Anstine
- Melyssa S. Roberts
- Parth R. Majmudar
- Ruth A Keri
- Viviane S. Finke
Organizations
- National Cancer Institute
- National Institutes of Health
- United States Department of Defense