Necroptosis in human cancers with special emphasis on oral squamous cell carcinoma

Abstract

Necroptosis is a type of caspase independent ‘programmed or regulated’ necrotic cell death that has a morphological resemblance to necrosis and mechanistic analogy to apoptosis. This type of cell death requires RIPK1, RIPK3, MLKL, death receptors, toll like receptors, interferons, and various other proteins. Necroptosis is implicated in plethora of diseases like rheumatoid arthritis, Alzheimer's disease, Crohn's disease, and head and neck cancers including oral squamous cell carcinoma. Oral carcinomas show dysregulation or mutation of necroptotic proteins, mediate antitumoral immunity, activate immune response and control tumor progression. Necroptosis is known to play a dual role (pro tumorigenic and anti-tumorigenic) in cancer progression and targeting this pathway could be an effective approach in cancer therapy. Necroptosis based chemotherapy has been proposed in malignancies, highlighting the importance of necroptotic pathway to overcome apoptosis resistance and serve as a “fail-safe” pathway to modulate cancer initiation, progression, and metastasis. However, there is dearth of information regarding the use of necroptotic cell death mechanism in the treatment of oral squamous cell carcinoma. In this review, we summarise molecular mechanism of necroptosis, and its protumorigenic and antitumorigenic role in cancers to shed light on the possible therapeutic significance of necroptosis in oral squamous cell carcinoma.