American Association for Cancer Research
00085472can140298-sup-126444_2_supp_0_n97wpj.docx (43.09 kB)

Data Supplement from EFA6B Antagonizes Breast Cancer

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journal contribution
posted on 2023-03-30, 22:45 authored by Joséphine Zangari, Mariagrazia Partisani, François Bertucci, Julie Milanini, Ghislain Bidaut, Carole Berruyer-Pouyet, Pascal Finetti, Elodie Long, Frédéric Brau, Olivier Cabaud, Bruno Chetaille, Daniel Birnbaum, Marc Lopez, Paul Hofman, Michel Franco, Frédéric Luton

Supplementary Table. Description of the datasets used for EFA6B/PSD4 mRNA expression analysis in breast cancer samples



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