Necroptosis signalling pathway in hepatic fibrosis; role of receptor-interacting serine-threonine kinase 3 and mixed lineage kinase domain-like in cirrhosis

Depletion of MLKL inhibits invasion of radioresistant nasopharyngeal carcinoma cells by suppressing epithelial-mesenchymal transition

“…In line with these observations, the radioresistant NPC cells (CR) generated by continuous irradiation of CNE-2 cells showed EMT and a higher degree of invasion as well as metastasis in the present study. While the role of MLKL in EMT has not been investigated in tumors so far, its activated (phosphorylated) form has been implicated in EMT during hepatic fibrosis as blocking necrosome formation with necrosulfonamide that prevents activation and translocation MLKL to the cell membrane suppressed mesenchymal phenotype of hepatic stellate cell (LX-2) (24). In the present study, EMT in CR was inhibited by MLKL depletion with either siRNA or CRISPER-Cas9 (CR-MLKL KO) indicating a possible involvement of MLKL in EMT and invasion.…”

“…For example, a negative relationship between p-MLKL and E-cadherin was observed in intestinal mucosal samples of pediatric patients with inflammatory bowel disease, while activated MLKL was found to alter E-cadherin and reduce cell-cell adhesion in vitro (23). On the other hand, necrosulfonamide, a pharmacological inhibitor of MLKL has been found to decrease α-SMA, coll1α, and vimentin expressions (involved in EMT) in LX-2 cell line and impair wound healing (24). However, it is unclear whether MLKL regulates invasion through EMT in any cancer cells.…”

“…Results of studies for non-cancer human diseases have suggested an association between MLKL and the regulators of epithelial/mesenchymal cell status (23,24). For example, a negative relationship between p-MLKL and E-cadherin was observed in intestinal mucosal samples of pediatric patients with inflammatory bowel disease, while activated MLKL was found to alter E-cadherin and reduce cell-cell adhesion in vitro (23).…”