Harshil has joined the lab. Harshil joined the Mercurio Lab as a summer undergraduate research student. Welcome to the Mercurio Lab!
WELCOME PETER!
Peter has joined the lab.
Peter joined the Mercurio Lab as a Research Associate. We are excited to have him aboard. Welcome!
OUR REVIEW ON VEGF/NEUROPILIN SIGNALING IN CANCER STEM CELLS WAS PUBLISHED IN THE INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES!
Mercurio AM. VEGF/Neuropilin Signaling in Cancer Stem Cells. Int J Mol Sci. 2019 Jan 23. PMID: 30678134
OUR REVIEW ON VEGF AND YAP/TAZ SIGNALING ON ANGIOGENESIS AND CANCER BIOLOGY IS OUT IN SCIENCE SIGNALING!
Elaimy AL, Mercurio AM. Convergence of VEGF and YAP/TAZ signaling: Implications for angiogenesis and cancer biology. Sci Signal. 2018 Oct 16. PMID: 30327408
OUR PAPER ON α6β4-PROMOTED FERROPTOSIS RESISTANCE IN MATRIX-DETACHED CELLS IS PUBLISHED IN JBC!
Abstract
Ferroptosis is an iron-dependent form of programmed cell death characterized by the accumulation of lipid-targeting reactive oxygen species that kill cells by damaging their plasma membrane. The lipid repair enzyme GSH peroxidase 4 (GPX4) protects against this oxidative damage and enables cells to resist ferroptosis. Recent work has revealed that matrix-detached carcinoma cells can be susceptible to ferroptosis and that they can evade this fate through the signaling properties of the α6β4 integrin, which sustains GPX4 expression. Although these findings on ferroptosis are provocative, they differ from those in previous studies indicating that matrix-detached cells are prone to apoptosis via a process referred to as anoikis. In an effort to reconcile these discrepant findings, here we observed that matrix-detached epithelial and carcinoma cells cluster spontaneously via a mechanism that involves the cell adhesion protein PVRL4 (also known as Nectin-4). We found that this clustering process allows these cells to survive by stimulating a PVRL4/α6β4/Src signaling axis that sustains GPX4 expression and buffers against lipid peroxidation. In the absence of α6β4, PVRL4-mediated clustering induced an increase in lipid peroxidation that was sufficient for triggering ferroptosis. When the clustering was inhibited, single cells did not exhibit a significant increase in lipid peroxidation in the absence of α6β4, and they were more susceptible to apoptosis than to ferroptosis. These results indicate that ferroptosis induction depends on cell clustering in matrix-detached cells that lack α6β4 and imply that the fate of matrix-detached cells can be determined by the state of their cell-cell interactions.
Brown CW, Amante JJ, Mercurio AM. Cell clustering mediated by the adhesion protein PVRL4 is necessary for α6β4 integrin-promoted ferroptosis resistance in matrix-detached cells. J Biol Chem. 2018 Aug 17. PMID: 29934307