Data from EFA6B Antagonizes Breast Cancer

• DOI: 10.1158/0008-5472.c.6506324.v1
• Publication Date: 2024-03-12T18:51:07Z
• Authors: Joséphine Zangari; Mariagrazia Parti...; François Bertucci; Julie Milanini; Ghislain Bidaut; Carole Berruyer-P...; Pascal Finetti; Elodie Long; Frédéric Brau; Olivier Cabaud; Bruno Chetaille; Daniel Birnbaum; Marc Lopez; Paul Hofman; Michel Franco; Frédéric Luton

<div>Abstract<p>One of the earliest events in epithelial carcinogenesis is dissolution tight junctions and cell polarity signals that are essential for normal barrier function. Here, we report EFA6B, a guanine nucleotide exchange factor Ras superfamily protein Arf6 helps assemble stabilize junction, required to maintain apico-basal mesenchymal phenotypes mammary cells. In organotypic three-dimensional cultures, endogenous levels EFA6B were critical determine epithelial–mesenchymal status. downregulation correlated with phenotype ectopic expression hampered TGFβ-induced epithelial-to-mesenchymal transition (EMT). Transcriptomic immunohistochemical analyses human breast tumors revealed reduced was associated loss junction components increased signatures EMT, cancer stemness, poor prognosis. Accordingly, low enriched aggressive triple-negative claudin-low subtypes. Our results identify as novel antagonist they point its regulatory signaling pathways rational therapeutic targets forms this disease. <i>Cancer Res; 74(19); 5493–506. ©2014 AACR</i>.</p></div>