MLKL-PITPα signaling-mediated necroptosis contributes to cisplatin-triggered cell death in lung cancer A549 cells

Cancer Letters
Lin JingZhinan Chen

Abstract

Necroptosis has been reported to be involved in cisplatin-induced cell death, but the mechanisms underlying the occurrence of necroptosis are not fully elucidated. In this study, we show that apart from apoptosis, cisplatin induces necroptosis in A549 cells. The alleviation of cell death by two necroptosis inhibitors-necrostatin-1 (Nec-1) and necrosulfonamide (NSA), and the phosphorylation of mixed lineage kinase domain-like protein (MLKL) at serine 358, suggest the involvement of receptor-interacting protein kinase 1 (RIPK1)-RIPK3-MLKL signaling in cisplatin-treated A549 cells. Additionally, the initiation of cisplatin-induced necroptosis relies on autocrine tumor necrosis factor alpha (TNF-α). Furthermore, we present the first evidence that phosphatidylinositol transfer protein alpha (PITPα) is involved in MLKL-mediated necroptosis by interacting with the N terminal MLKL on its sixth helix and the preceding loop, which facilitates MLKL oligomerization and plasma membrane translocation in necroptosis. Silencing of PITPα expression interferes with MLKL function and reduces cell death. Our data elucidate that cisplatin-treated lung cancer cells undergo a new type of programmed cell death called necroptosis and shed new light on ...Continue Reading

Citations

Jun 10, 2019·Apoptosis : an International Journal on Programmed Cell Death·Lin JingZhi-Nan Chen
Aug 17, 2019·American Journal of Physiology. Heart and Circulatory Physiology·Paras K MishraTakashi Matsui
Mar 29, 2020·Biomolecules·Brittany DewdneyLionel Hebbard
Aug 15, 2019·Experimental and Therapeutic Medicine·Aijun RenLiangjie Zheng
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Dec 16, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Heng-Long WangJer-Yiing Houng
Mar 22, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Shaoming JinFazheng Ren
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