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Necroptosis in human cancers with special emphasis on oral squamous cell carcinoma
Reshma Poothakulath Krishnan1, Deepak Pandiar1, Pratibha Ramani1
1Department of Oral Pathology and Microbiology, Saveetha Dental College and Hospitals, Chennai, Tamil Nadu.
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.
Insights
Necroptosis, a regulated cell death, is crucial in diseases like oral cancer. Targeting necroptosis offers a promising therapeutic strategy for oral squamous cell carcinoma.
Area of Science:
- Cellular biology
- Molecular mechanisms of cell death
- Oncology
Background:
- Necroptosis is a programmed necrotic cell death pathway requiring specific proteins like RIPK1, RIPK3, and MLKL.
- This cell death mechanism is implicated in various diseases, including rheumatoid arthritis, Alzheimer's, Crohn's disease, and head and neck cancers.
- Oral squamous cell carcinoma exhibits dysregulation of necroptosis proteins, influencing antitumoral immunity and tumor progression.
Approach:
- This review summarizes the molecular mechanisms of necroptosis.
- It examines the dual role of necroptosis in cancer progression (both pro- and anti-tumorigenic).
- The review highlights the potential therapeutic significance of targeting necroptosis in oral squamous cell carcinoma.
Key Points:
- Necroptosis plays a complex role in cancer, acting as both a promoter and inhibitor of tumor growth.
- Targeting necroptosis is a potential therapeutic strategy to overcome apoptosis resistance in malignancies.
- Necroptosis can serve as a "fail-safe" mechanism to control cancer initiation, progression, and metastasis.
Conclusions:
- There is a significant lack of information on utilizing necroptosis for oral squamous cell carcinoma treatment.
- Understanding necroptosis's molecular mechanisms and its role in cancer is vital for developing novel therapies.
- Targeting necroptosis presents a promising avenue for overcoming therapeutic resistance and improving outcomes in oral squamous cell carcinoma.
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