Blocking on the CXCR4/mTOR signalling pathway induces the anti-metastatic properties and autophagic cell death in peritoneal disseminated gastric cancer cells

Purpose: Golgi phosphoprotein-3 (GOLPH3) is an oncogene that is overexpressed in multiple cancers and is associated with poor prognosis. The aim of this study was to examine the impact of GOLPH3 on the migration and metastasis of gastric cancer cells. Methods: Following the shRNA-mediated knockdown of GOLPH3, we analyzed cytoskeletal reorganization and cell invasion, migration and adhesion, and determined the impact of components of the mammalian target of the rapamycin (mTOR) signalling pathway. Results: The GOLPH3 mRNA and protein expression were significantly lower in both SGC-7901 and MKN-28 cells as compared with poorly-differentiated BGC-823 cells. The GOLPH3 knockdown also significantly reduced cell invasion in all three cell lines through reduced migration as compared with the non-targeting control sequence group. The GOLPH3 knockdown also reduced F-actin in all three cell lines, and decreased cell adhesion in BGC-823 and SGC-7901 cells. Finally, p-mTOR, p70S6K, p-4EBP1 and RhoA protein levels were significantly downregulated in shGOLPH3-1-treated cells. Conclusions: In conclusion, GOLPH3 increased in poorly-differentiated gastric cancer cells, activating the mTOR-70S6K/4EBP1-RhoA signalling pathway to promote the migration and metastasis of gastric cancer cells.

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miR-3174 Contributes to Apoptosis and Autophagic Cell Death Defects in Gastric Cancer Cells by Targeting ARHGAP10

Molecular Therapy — Nucleic Acids ◽

10.1016/j.omtn.2017.10.008 ◽

2017 ◽

Vol 9 ◽

pp. 294-311 ◽

Cited By ~ 17

Author(s):

Bowen Li ◽

Lu Wang ◽

Zheng Li ◽

Weizhi Wang ◽

Xiaofei Zhi ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Death ◽

Cancer Cells ◽

Autophagic Cell Death ◽

Gastric Cancer Cells

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Moxidectin induces Cytostatic Autophagic Cell Death of Glioma Cells through inhibiting the AKT/mTOR Signalling Pathway

Journal of Cancer ◽

10.7150/jca.46697 ◽

2020 ◽

Vol 11 (19) ◽

pp. 5802-5811

Author(s):

Jingjing Liu ◽

Hongsheng Liang ◽

Saadia Khilji ◽

Haitao Li ◽

Dandan Song ◽

...

Keyword(s):

Cell Death ◽

Glioma Cells ◽

Signalling Pathway ◽

Autophagic Cell Death ◽

Mtor Signalling ◽

Mtor Signalling Pathway

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Cinnamaldehyde induces autophagy-mediated cell death through ER stress and epigenetic modification in gastric cancer cells

Acta Pharmacologica Sinica ◽

10.1038/s41401-021-00672-x ◽

2021 ◽

Author(s):

Tae Woo Kim

Keyword(s):

Gastric Cancer ◽

Cell Death ◽

Er Stress ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Epigenetic Modification ◽

Autophagic Cell Death ◽

Beclin 1 ◽

Gastric Cancer Cells ◽

Autophagy Inhibition

AbstractPrevious reports suggested that cinnamaldehyde (CA), the bioactive ingredient in Cinnamomum cassia, can suppress tumor growth, migratory, and invasive abilities. However, the role and molecular mechanisms of CA in GC are not completely understood. In the present study, we found that CA-induced ER stress and cell death via the PERK–CHOP axis and Ca2+ release in GC cells. Inhibition of ER stress using specific–siRNA blocked CA-induced cell death. Interestingly, CA treatment resulted in autophagic cell death by inducing Beclin-1, ATG5, and LC3B expression and by inhibiting p62 expression whereas autophagy inhibition suppressed CA-induced cell death. We showed that CA induces the inhibition of G9a and the activation of LC3B. Moreover, CA inhibited G9a binding on Beclin-1 and LC3B promoter. Overall, these results suggested that CA regulates the PERK–CHOP signaling, and G9a inhibition activates autophagic cell death via ER stress in GC cells.

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