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TNF-α, and TNFRs in gastrointestinal cancers
Zahra Mozooni1, Rezvaneh Ghadyani2, Shahrzad Soleimani3
1Institute of Immunology and Infectious Diseases, Antimicrobial Resistance Research Center, Iran University of Medical Sciences, Tehran, Iran.
Pathology, Research and Practice
|October 23, 2024
Summary
Tumor necrosis factor-alpha (TNF-α), a key immune regulator, paradoxically fuels digestive cancers by promoting inflammation and cell growth. Understanding its role is crucial for developing new cancer therapies.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Tumor necrosis factor-alpha (TNF-α) is a critical cytokine involved in immune responses, inflammation, and cell proliferation.
- Dysregulation of TNF-α contributes to chronic inflammatory diseases and various cancers, including digestive malignancies.
- Gastrointestinal cancers represent a significant global health burden with poor prognoses and late-stage detection.
Purpose of the Study:
- To review the multifaceted role of TNF-α and its receptors in the pathogenesis of digestive cancers.
- To elucidate the signaling pathways and molecular functions of TNF-α implicated in gastrointestinal tumor development.
- To highlight the contribution of TNF-α and associated cytokines within the tumor microenvironment.
Main Methods:
- Literature review of studies on TNF-α, its receptors (TNFR1, TNFR2), and signaling pathways (TRAFs, NF-κB, AP-1).
- Analysis of the involvement of TNF-α in cellular processes relevant to cancer, including proliferation, apoptosis, and inflammation.
- Examination of the impact of TNF-α on the tumor microenvironment and its association with digestive cancer progression.
Main Results:
- TNF-α signaling, through TNFR1 and TNFR2, activates transcription factors like NF-κB and AP-1, promoting pro-inflammatory and pro-survival pathways.
- While TNF-α can induce apoptosis via specific receptor interactions (e.g., Fas Ligand), its role in cancer often involves promoting cell growth and inflammation.
- Cytokines, including TNF-α, are recognized as key players in the tumor microenvironment, driving the development and metastasis of digestive cancers.
Conclusions:
- TNF-α and its receptors are pivotal in the complex mechanisms underlying digestive cancer development.
- Targeting TNF-α signaling pathways presents a potential therapeutic strategy for gastrointestinal malignancies.
- Further research into TNF-α's dual role is essential for effective cancer treatment and prevention.
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