OUR PAPER ON PROMININ2'S ROLE IN FERROPTOSIS RESISTANCE IS PUBLISHED IN DEVELOPMENTAL CELL!

ABSTRACT

Ferroptosis, regulated cell death characterized by the iron-dependent accumulation of lethal lipid reactive oxygen species, contributes to tissue homeostasis and numerous pathologies, and it may be exploited for therapy. Cells differ in their sensitivity to ferroptosis, however, and a key challenge is to understand mechanisms that contribute to resistance. Using RNA-seq to identify genes that contribute to ferroptosis resistance, we discovered that pro-ferroptotic stimuli, including inhibition of the lipid hydroperoxidase GPX4 and detachment from the extracellular matrix, induce expression of prominin2, a pentaspanin protein implicated in regulation of lipid dynamics. Prominin2 facilitates ferroptosis resistance in mammary epithelial and breast carcinoma cells. Mechanistically, prominin2 promotes the formation of ferritin-containing multivesicular bodies (MVBs) and exosomes that transport iron out of the cell, inhibiting ferroptosis. These findings reveal that ferroptosis resistance can be driven by a prominin2-MVB-exosome-ferritin pathway and have broad implications for iron homeostasis, intracellular trafficking, and cancer.

 
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Brown CW, Amante JJ, Chhoy P, Elaimy AL, Haibo L, Zhu LJ, Baer CE, Dixon SJ, Mercurio AM. Prominin2 Drives Ferroptosis Resistance by Stimulating Multivesicular Body/Exosome-Mediated Iron Export. Developmental Cell. 14 November 2019.

OUR PAPER ON REAL-TIME IMAGING OF INTEGRIN β4 DYNAMICS USING A REPORTER CELL LINE IS OUT IN THE JOURNAL OF CELL SCIENCE!

Abstract

The ability to monitor changes in the expression and localization of integrins is essential for understanding their contribution to development, tissue homeostasis and disease. Here, we pioneered the use of Crispr/Cas9 genome editing to tag an allele of the β4 subunit of the α6β4 integrin. A tdTomato tag was inserted with a linker at the C-terminus of integrin β4 in mouse mammary epithelial cells. Cells harboring this tagged allele were similar to wild-type cells with respect to integrin β4 surface expression, association with the α6 subunit, adhesion to laminin and consequent signaling. These integrin β4 reporter cells were transformed with YAP (also known as YAP1), which enabled us to obtain novel insight into integrin β4 dynamics in response to a migratory stimulus (scratch wound) by live-cell video microscopy. An increase in integrin β4 expression in cells proximal to the wound edge was evident, and a population of integrin β4-expressing cells that exhibited unusually rapid migration was identified. These findings could shed insight into integrin β4 dynamics during invasion and metastasis. Moreover, these integrin β4 reporter cells should facilitate studies on the contribution of this integrin to mammary gland biology and cancer.This article has an associated First Person interview with the first author of the paper.

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Elaimy AL, Wang M, Sheel A, Brown CW, Walker MR, Amante JJ, Xue W, Chan A, Baer CE, Goel HL, Mercurio AM. Real-time imaging of integrin β4 dynamics using a reporter cell line generated by Crispr/Cas9 genome editing. J Cell Sci. 2019 Jul 31. PMID: 31262785

AMEER'S PAPER ON VEGFR NEUROPILIN 2 PROMOTION OF HOMOLOGOUS RECOMBINATION BY STIMULATING YAP/TAZ-MEDIATED RAD51 EXPRESSION IS OUT IN PNAS!

Elaimy AL, Amante JJ, Zhu LJ, Wang M, Walmsley CS, FitzGerald TJ, Goel HL, Mercurio AM. The VEGF receptor neuropilin 2 promotes homologous recombination by stimulating YAP/TAZ-mediated Rad51 expression. Proc Natl Acad Sci U S A. 2019 Jul 9. PMID: 31235595

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