Project Details
Projekt
cPLA2α-mediated ferroptosis regulation in small cell lung cancer (SCLC)
Applicant
Professorin Dr. Silvia von Karstedt
Subject Area
Cell Biology
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 461704389
Small cell lung cancer (SCLC) is amongst the most aggressive forms of lung cancer with a very poor survival rate due to rapidly emerging chemotherapy resistance. Previously, we identified non-neuroendocrine (non-NE) SCLC to be exquisitely sensitive to ferroptosis while upon NE transdifferentiation/plasticity SCLC became ferroptosis resistant. Moreover, we defined a first atlas of ferroptotic secretomes capable of promoting macrophage priming. In addition, we previously found that during ferroptosis there is an early calcium influx preceding cell death. Recently, we found that cPLA2α expression is highly upregulated in ferroptosis sensitive human and mouse non-NE SCLC and promotes faster kinetics of ferroptotic cell death through the generation of free arachidonic acid (AA). Based on these data, with this proposal we aim to comprehensively discern how AA flux influences ferroptosis kinetics in cellular models of SCLC subtype heterogeneity and plasticity.
DFG Programme
Priority Programmes
