Dear Editor,

Foci of cell death are commonly observed in core regions of solid tumors as a result of inadequate vascularization and subsequent metabolic stresses such as hypoxia and glucose deprivation. Since the morphology of dead tumor cells appears to be necrotic, it is often referred as tumor necrosis. Tumor necrosis has been found to be associated with tumorigenesis and poor prognosis for years,1 but the role of necrosis in tumor development is still largely unknown. Additionally, the molecular mechanism of necrosis is an under-studied area due to the lack of experimental system for manipulating necrotic cell death. Necroptosis is a form of programmed, caspase-independent necrosis.2 Studies on TNF-induced necroptosis have improved our understanding on the molecular mechanism of necroptosis. It is now known that the protein kinases receptor interacting protein kinase 1 (RIPK1), RIPK3 and the mixed lineage kinase domain-like (MLKL) constitute the core of the necroptosis machinery.3,4,5 Importantly, RIPK3-mediated phosphorylation of MLKL results in MLKL oligomerization and its subsequent translocation to the plasma membrane.6 Necroptotic pathway may be involved in tumorigenesis,7,8 yet it is not clear if tumor cells undergo necroptosis during tumor development and if so, what role does necroptosis play in tumorigenesis and tumor metastasis. In this study, we demonstrated that necroptosis of tumor cells is responsible for tumor necrosis and is critical for metastasis.

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