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Biological Functions of Gasdermins in Cancer: From Molecular Mechanisms to Therapeutic Potential
Man Wang1, Xinzhe Chen1, Yuan Zhang1
1Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China.
Abstract:
Pyroptosis is a type of lytic programmed cell death triggered by various inflammasomes that sense danger signals. Pyroptosis has recently attracted great attention owing to its contributory role in cancer. Pyroptosis plays an important role in cancer progression by inducing cancer cell death or eliciting anticancer immunity. The participation of gasdermins (GSDMs) in pyroptosis is a noteworthy recent discovery. GSDMs have emerged as a group of pore-forming proteins that serve important roles in innate immunity and are composed of GSDMA-E and Pejvakin (PJVK) in human. The N-terminal domains of GSDMs, expect PJVK, can form pores on the cell membrane and function as effector proteins of pyroptosis. Remarkably, it has been found that GSDMs are abnormally expressed in several forms of cancers. Moreover, GSDMs are involved in cancer cell growth, invasion, metastasis and chemoresistance. Additionally, increasing evidence has indicated an association between GSDMs and clinicopathological features in cancer patients. These findings suggest the feasibility of using GSDMs as prospective biomarkers for cancer diagnosis, therapeutic intervention and prognosis. Here, we review the progress in unveiling the characteristics and biological functions of GSDMs. We also focus on the implication and molecular mechanisms of GSDMs in cancer pathogenesis. Investigating the relationship between GSDMs and cancer biology could assist us to explore new therapeutic avenues for cancer prevention and treatment.
Insights
Gasdermins (GSDMs) are key proteins in pyroptosis, a cell death process crucial for cancer immunity and progression. Their abnormal expression in cancer suggests potential as diagnostic and therapeutic biomarkers.
Area of Science:
- Cell Biology
- Immunology
- Oncology
Background:
- Pyroptosis is programmed cell death triggered by inflammasomes, playing a role in cancer progression by inducing cell death and anticancer immunity.
- Gasdermins (GSDMs) are pore-forming proteins essential for pyroptosis, with abnormal expression observed in various cancers.
Purpose of the Study:
- To review the characteristics and biological functions of GSDMs.
- To explore the implications and molecular mechanisms of GSDMs in cancer pathogenesis.
- To highlight the potential of GSDMs as biomarkers for cancer diagnosis, therapy, and prognosis.
Main Methods:
- Literature review of GSDM research in cancer biology.
- Analysis of GSDM involvement in cancer cell death, growth, invasion, metastasis, and chemoresistance.
- Examination of the association between GSDMs and clinicopathological features in cancer patients.
Main Results:
- GSDMs function as effector proteins in pyroptosis by forming pores on cell membranes.
- Abnormal GSDM expression is linked to cancer progression, affecting cell growth, invasion, metastasis, and chemoresistance.
- GSDMs show associations with cancer clinicopathological features, indicating biomarker potential.
Conclusions:
- GSDMs are critical regulators of pyroptosis with significant roles in cancer biology.
- GSDMs represent promising biomarkers for cancer diagnosis, prognosis, and therapeutic intervention.
- Further investigation into GSDMs and cancer biology may reveal new therapeutic strategies.
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