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Golgicide A induces pyroptosis of lung cancer stem cells by regulating dTGN formation via GOLPH3/MYO18A complex
Feng Zhang1, Sun-Han Zhang1, Teng Liu1
1School of Clinical Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu, 610500, China.
Background:
Lung cancer is a common malignant neoplasm, one of the leading causes of death worldwide. Cancer stem cells (CSCs) drive tumor recurrence, progression, and therapeutic resistance. Thus, targeting CSCs may contribute to lung cancer treatment and improve clinical outcomes.
Methods:
We induced stem cell formation in serum-free suspension culture. Cell viability was assessed using the cell counting-kit 8 assay, and cell membrane integrity was evaluated using the lactate dehydrogenase release assay. Caspase-1 activity assays, western blotting, enzyme-linked immunosorbent assay, and flow cytometry were used to analyze pyroptosis in cells. Confocal microscopy was used to detect protein co-localization. Quantification of fluorescence intensity and co-localization was carried out using ImageJ software. Co-immunoprecipitation was performed to assess the interaction between GOLPH3 and MYO18A. An animal study was conducted to evaluate the effects of golgicide A (GCA) on tumor growth in vivo.
Results:
GCA induced cell death via pyroptosis in both H1650- and A549-derived CSCs. GCA enhanced the binding of GOLPH3 and MYO18A, resulting in trans-Golgi network (TGN) dispersion. In turn, the dispersed TGN (dTGN) recruited NLRP3. Our xenograft animal model study confirmed that GCA can inhibit tumor growth.
Conclusions:
GCA induced pyroptosis by promoting the interaction between GOLPH3 and MYO18A, resulting in dTGN formation in lung CSCs. Our findings provide a novel molecular insight into the anti-cancer activities of GCA in lung CSCs.
Insights
Golgicide A (GCA) induces pyroptosis in lung cancer stem cells (CSCs) by promoting GOLPH3 and MYO18A interaction, leading to trans-Golgi network dispersion. This novel mechanism inhibits tumor growth, offering a potential new strategy for lung cancer treatment.
Area of Science:
- Oncology
- Cell Biology
- Molecular Medicine
Background:
- Lung cancer remains a leading cause of cancer-related mortality globally.
- Cancer stem cells (CSCs) are implicated in tumor recurrence, progression, and resistance to therapy.
- Targeting CSCs presents a promising strategy to improve lung cancer treatment outcomes.
Purpose of the Study:
- To investigate the molecular mechanisms by which golgicide A (GCA) affects lung cancer stem cells (CSCs).
- To evaluate the therapeutic potential of GCA in inhibiting lung CSCs and tumor growth.
Main Methods:
- Induction of stem cell formation in vitro.
- Assessment of cell viability, membrane integrity, and pyroptosis using various assays (CCK-8, LDH, Caspase-1 activity, Western blotting, ELISA, flow cytometry).
- Analysis of protein co-localization and interactions (confocal microscopy, co-immunoprecipitation).
- In vivo evaluation of GCA efficacy in a xenograft mouse model.
Main Results:
- Golgicide A (GCA) induced cell death via pyroptosis in lung cancer stem cells (CSCs).
- GCA treatment enhanced the interaction between GOLPH3 and MYO18A, leading to trans-Golgi network (TGN) dispersion.
- The dispersed TGN (dTGN) recruited NLRP3, and GCA inhibited tumor growth in vivo.
Conclusions:
- Golgicide A (GCA) triggers pyroptosis in lung CSCs by modulating GOLPH3-MYO18A interaction and inducing dTGN formation.
- These findings elucidate a novel molecular pathway for GCA's anti-cancer activity in lung CSCs.
- GCA demonstrates potential as a therapeutic agent for targeting lung cancer stem cells.
