FGFR2c-TRPA1 Lipid Raft Signaling In PDAC Progression

A recent Cell Death & Disease study by Mancini et al. demonstrates that ligand-activated FGFR2c is dynamically recruited into cholesterol-rich lipid raft microdomains, where it drives oncogenic signaling through interaction with the TRPA1 channel (1). Lipid raft disruption using methyl-β-cyclodextrin (MβCD), or TRPA1 depletion, markedly suppressed activation of the PKCε, ERK1/2, mTOR, and SRC signaling cascades, resulting in reversal of the EMT phenotype and attenuation of MCL1/SRC-dependent invasive behavior in FGFR2c-high PDAC cells.

This study demonstrates that TRPA1 contributes to FGFR2c recruitment to intact lipid rafts and the establishment of the FGFR2c-PKCe-ERK1/2 oncogenic signaling axis, thereby highlighting FGFRs, TRPA1, and lipid rafts as compelling candidates for further investigation and possible development of combinatorial and tumor-specific therapeutic strategies targeting PDAC and other malignancies.