Targeting AREG and EREG to Inhibit Proliferation and Enhance Therapeutic Efficacy in Breast Cancer
Year: 2025
Type: article
Abstract: The deregulation of Epidermal Growth Factor Receptor (EGFR) signaling via autocrine ligands is a hallmark of breast cancer progression and therapeutic resistance. Amphiregulin (AREG) and Epiregulin (EREG) are frequently overexpressed; however, their distinct contributions to tumor growth and drug sensitivity across different cancer subtypes remain to be fully understood. Here, we profiled the expression patterns of AREG and EREG in HCT116, HeLa, and breast cancer cell lines. Employing CRISPR-Cas9 gene-editing systems we established knockout models to determine the functional necessity of these ligands in breast cancer pathology. We demonstrate that the genetic ablation of AREG or EREG significantly impairs tumorigenic potential, resulting in an 89% reduction in cell growth in triple-negative MDA-MB-231 cells and a 42% reduction in MCF7 cells. Furthermore, we reveal that the targeting of these ligands synergistically enhances the therapeutic efficacy of tamoxifen, effectively overcoming growth mechanisms in breast cancer cells. These findings underscore the critical role of AREG and EREG as drivers of breast cancer proliferation and suggest that their inhibition, particularly in combination with endocrine therapy, represents a promising strategy to improve clinical outcomes.
Authors: Young Eun Kim, Sun-Ji Park, Euihwan Choi
Language: English
Topic: HER2/EGFR in Cancer Research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7125843436