. Cellular reprogramming via ID4 manipulation: a novel approach to tackle triple negative breast cancer

TORO, CARLA; REAL, SEBASTIAN; LAURITO SERGIO; ROQUÉ, MARÍA; BRANHAM MARIA TERESITA

Mar del Plata

Congreso; Sociedad Argentina de Investigación Clínica (SAIC); 2023

Background: This study focuses on exploring the potential capacity of ID4 to reprogram triple negative breast tumors, a novel approach given the limited treatment options for triple negative breast cancer (TNBC). To address this, we focus on cell plasticity as a strategic possibility. This involves the reprogramming of TN tumors into luminal subtypes, thereby sensitizing them to endocrine therapies. Notably, ID4, an inhibitor of differentiation protein, assumes a central role in the reprogramming of mammary cells by controlling the transcription of lineage-specific genes. We hypothesize that the manipulation of ID4 expression could revert aggressive features of TN tumors by triggering luminal differentiation. Methods: In-silico analyses involved the evaluation of ID4 expression on human TN breast tumors of public datasets. In vitro experiments involved cell culture of MDAMB231 estrogen receptor (ER-) breast cancer cell lines, ID4 expression was silenced by CRISPR-Cas9 technology. Gene and protein expression were analyzed by RT-qPCR and western blot. Results: In silico analysis stratifying ID4 expression in TN breast cancer tumors into “high” and “low” groups reveals distinct luminal and basal gene expression patterns. Notably, the low ID4 group exhibits a significant upregulation in luminal signature expression (p