Tanshinone IIA Reverses the Malignant Phenotype of SGC7901 Gastric Cancer Cells

This article is aimed at exploring the relationship between the phosphatase 2A catalytic subunit Cα (PP2Acα, encoded by PPP2CA) and methyltransferase-like 3 (METTL3) in the malignant progression of gastric cancer (GC). Through analyzing the bioinformatics database and clinical tissue immunohistochemistry results, we found that abnormal PP2Acα and METTL3 levels were closely related to the malignant progression of GC. To explore the internal connection between PP2Acα and METTL3 in the progression of GC, we carried out cellular and molecular experiments and finally proved that PP2Acα inhibition can upregulate METTL3 levels by activating ATM activity, thereby promoting the malignant progression of GC.

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Production of trypsins by human gastric cancer cells correlates with their malignant phenotype

European Journal of Cancer ◽

10.1016/s0959-8049(98)00077-x ◽

1998 ◽

Vol 34 (7) ◽

pp. 1117-1123 ◽

Cited By ~ 31

Author(s):

Y Kato ◽

Y Nagashima ◽

N Koshikawa ◽

Y Miyagi ◽

H Yasumitsu ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Human Gastric Cancer ◽

Malignant Phenotype ◽

Gastric Cancer Cells

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Reversal of the Malignant Phenotype of Gastric Cancer Cells by Inhibition of RhoA Expression and Activity

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-04-0242 ◽

2004 ◽

Vol 10 (18) ◽

pp. 6239-6247 ◽

Cited By ~ 67

Author(s):

Na Liu ◽

Feng Bi ◽

Yanglin Pan ◽

Lijun Sun ◽

Yan Xue ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Malignant Phenotype ◽

Gastric Cancer Cells ◽

Expression And Activity

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Abnormal N-glycosylated CPXM1 promotes gastric cancer metastasis through ITGB2 / FAK pathway

10.21203/rs.3.rs-613113/v1 ◽

2021 ◽

Author(s):

Jun Du ◽

Mengxiang Zhu ◽

Wenwu Yan ◽

Jin Guo Wang

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Bioinformatics Analysis ◽

Abdominal Cavity ◽

Migration And Invasion ◽

Signal Pathways ◽

Malignant Phenotype ◽

Gastric Cancer Cells ◽

Glycosylation Sites

Abstract Background: To explore the molecular mechanism of CPXM1 in gastric cancer (GC) metastasis.Methods: Based on the difference in expression of CPXM1 mRNA in GC tissues and normal gastric mucosa tissues in public databases, rt-PCR, WB and IHC staining experiments were performed to verify the expression of CPXM1 in fresh GC tissues. Bioinformatics analysis predicts the possible signal pathways of co-expression genes in CPXM1 overexpression group. The malignant phenotypes of GC cells was verified by in vivo and in vitro experiments. Using tunicamycin to inhibit the N-glycosylation of CPXM1 and constructing mutations. The plasmid further validated the specific N-glycosylation sites that affect the malignant phenotype of gastric cancer cells.Results: CPXM1 mRNA expression was significantly increased in GC tissues. The results of IHC staining and WB indicated that there was no difference in the expression of CPXM1 at the protein level. Knocking down CPXM1 expression in HGC-27 cells can significantly inhibit its migration and invasion ability. Increasing the expression of CPXM1 in MGC-803 and BGC-823 cell lines can significantly promote its migration and invasion capabilities. CPXM1 can also promote the adhesion of GC cells and change the cytoskeleton structure. The results of in-vivo experiments show that CPXM1 can promote the metastasis of GC cells in the abdominal cavity of nude mice. Bioinformatics analysis showed that the co-expressed genes of the CPXM1 high expression group were mainly enriched in cell adhesion function, and the experimental results verified that CPXM1 may promote the adhesion and metastasis of gastric cancer cells through the ITGB2/FAK signaling pathway. Through N-glycosylation site prediction and WB results, it was found that CPXM1 had abnormal N-glycosylation in GC tissues. Tunicamycin can reverse the ability of CPXM1 that promote the invasion of GC cells. After respectively mutating the N-glycosylation sites on CPXM1, it was found that N210 site is the key site for CPXM1 to promote the adhesion and invasion of GC cells.Conclusion: CPXM1 is upgraded in GC. CPXM1 can promote the adhesion, migration and invasion of GC cells and change cytoskeleton structure. The N210 site on CPXM1 is a key site affecting the malignant phenotype of GC.

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Tanshinone IIA induces ferroptosis in gastric cancer cells through p53-mediated SLC7A11 down-regulation

Bioscience Reports ◽

10.1042/bsr20201807 ◽

2020 ◽

Vol 40 (8) ◽

Cited By ~ 1

Author(s):

Zhenhua Guan ◽

Jing Chen ◽

Xueliang Li ◽

Na Dong

Keyword(s):

Gastric Cancer ◽

Lipid Peroxidation ◽

Cancer Cells ◽

Salvia Miltiorrhiza ◽

Chinese Herb ◽

Tanshinone Iia ◽

Gastric Cancer Cells ◽

P53 Expression ◽

Anti Cancer ◽

Pharmacologically Active

Abstract Gastric cancer represents a malignant type of cancer worldwide. Tanshinone IIA (Tan IIA), a pharmacologically active component isolated from the rhizome of the Chinese herb Salvia miltiorrhiza Bunge (Danshen), has been reported to possess an anti-cancer effect in gastric cancer. However, its mechanisms are still not fully understood. In the present study, we found that Tan IIA induced ferroptosis in BGC-823 and NCI-H87 gastric cancer cells. Tan IIA increased lipid peroxidation and up-regulated Ptgs2 and Chac1 expression, two markers of ferroptosis. Ferrostatin-1 (Fer-1), an inhibitor of lipid peroxidation, inhibited Tan IIA caused-lipid peroxidation and Ptgs2 and Chac1 expression. In addition, Tan IIA also up-regulated p53 expression and down-regulated xCT expression. Tan IIA caused decreased intracellular glutathione (GSH) level and cysteine level and increased intracellular reactive oxygen species (ROS) level. p53 knockdown attenuated Tan IIA-induced lipid peroxidation and ferroptosis. Tan IIA also induced lipid peroxidation and ferroptosis in BGC-823 xenograft model, and the anti-cancer effect of Tan IIA was attenuated by Fer-1 in vivo. Therefore, Tan IIA could suppress the proliferation of gastric cancer via inducing p53 upregulation-mediated ferroptosis. Our study have identified a novel mechanism of Tan IIA against gastric cancer, and might provide a critical insight into the application of Tan IIA in gastric cancer intervention.

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