Podcast
Questions and Answers
What is the term for a form of programed cell death that is induced by inflammatory caspases?
What is the term for a form of programed cell death that is induced by inflammatory caspases?
Pyroptosis
What is the name of the signaling pathway involved in oral squamous cell carcinoma progression?
What is the name of the signaling pathway involved in oral squamous cell carcinoma progression?
JAK2/STAT3/Sox4/NLRP3
What is the term for the complex secretory program orchestrated by the inflammasome?
What is the term for the complex secretory program orchestrated by the inflammasome?
Paracrine senescence
What is the name of the protein that is cleaved by inflammatory caspases, leading to pyroptotic cell death?
What is the name of the protein that is cleaved by inflammatory caspases, leading to pyroptotic cell death?
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What is the term for the cellular state characterized by permanent cell cycle arrest and the secretion of pro-inflammatory factors?
What is the term for the cellular state characterized by permanent cell cycle arrest and the secretion of pro-inflammatory factors?
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What is the name of the protein complex involved in inflammasome activation?
What is the name of the protein complex involved in inflammasome activation?
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What is the term for the SASP-mediated promotion of tumor growth and metastasis?
What is the term for the SASP-mediated promotion of tumor growth and metastasis?
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What is the name of the cytokine involved in inflammasome activation and pyroptosis?
What is the name of the cytokine involved in inflammasome activation and pyroptosis?
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What is the term for the role of the SASP in atherosclerosis?
What is the term for the role of the SASP in atherosclerosis?
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What is the name of the cellular process characterized by cell lysis and the release of pro-inflammatory mediators?
What is the name of the cellular process characterized by cell lysis and the release of pro-inflammatory mediators?
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Study Notes
Pyroptosis in Cancer
- The role of pyroptosis in cancer is not well understood, but evidence suggests it may play a tumor-suppressive role in melanomas and breast cancers.
SASP CM-mediated Pyroptosis
- Senescent fibroblasts can induce pyroptosis in mammary epithelial cells through SASP CM (senescence-associated secretory phenotype conditioned medium).
- Oncogene expression in normal mammary epithelial cells can prevent SASP CM-mediated cell death, suggesting senescent fibroblasts may eliminate cells that could become cancerous.
Implications of Senolytic Agents
- Senolytic agents, which eliminate senescent cells, may inadvertently remove a mechanism of tumor suppression, highlighting the need to better understand the role of SASP CM-mediated pyroptosis in different cell types and disease contexts.
Cell Culture and Experimental Procedures
- Various cell lines were used, including MCF-10A, BJ human foreskin fibroblasts, MDA-MB-231, MDA-MB-436, HMEC, HuVEC, and KTB-34.
- Cells were cultured in specific media and supplemented with various growth factors and antibiotics.
- Reagents used included z-VAD-fmk, staurosporine, MCC950, Sytox Green, and Hoechst 33342.
Lentiviral Delivery of shRNA
- Lentiviral vectors were used to deliver shRNA constructs against CASP8, CASP1, and GSDMD to generate stable knockdown cell lines.
- Puromycin selection was used to obtain stable populations of puromycin-resistant cells.
Immunoblots and Microscopy
- Immunoblots were performed to confirm knockdowns of CASP1 and GSDMD.
- Immunofluorescence microscopy was used to image cells stained with Hoechst and SYTOX Green to quantify the percentage of SYTOX Green-positive cells.
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Description
Explore the emerging role of pyroptosis in cancer, particularly as a tumor suppressive mechanism in melanomas and breast cancers. Understand the implications of SASP CM-mediated pyroptosis in different cell types and disease contexts for physiological and pathological conditions. Reflect on potential therapeutic strategies and their impacts on pyroptosis in cancer treatment.
