Project Details
Projekt
Consequences of 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. Recently, we identified non-neuroendocrine (NE) SCLC to be exquisitely sensitive to ferroptosis while upon NE transdifferentiation SCLC became ferroptosis resistant. Interestingly, our preliminary data identify elevated expression of cellular phospholipase 2α (cPLA2α) as a marker of ferroptosis sensitivity and its inhibition to blocks ferroptosis induction. Based on these data we hypothesise that cPLA2α may be activated during ferroptosis and promote cell death induction, lipid mediator synthesis and tumour associated inflammation. Therefore, with this proposal we aim to comprehensively characterise the role of cPLA2α in regulating ferroptosis and cancer-associated inflammation in SCLC. In more detail, we propose to undertake work pertaining to the following three aims:Aim 1: Elucidate mechanisms of cPLA2α-mediated ferroptosis promotion Aim 2: Determine the role of cPLA2α-induced lipid mediator synthesis in ferroptosisAim 3: Characterising ferroptosis-associated inflammation in SCLC at single cell resolution By addressing these three aims, we anticipate to unravel how cPLA2α integrates with ferroptotic cell death and inflammatory signalling in SCLC.
DFG Programme
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