scholarly journals Apolipoprotein C-II induces EMT to Promote Gastric Cancer Peritoneal Metastasis via PI3K/AKT/mTOR Pathway

2021 ◽  
Author(s):  
Chao Wang ◽  
Zhi Yang ◽  
En Xu ◽  
Xingzhou Wang ◽  
Zijian Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Lipid Metabolism ◽  
Signaling Pathway ◽  
Peritoneal Metastasis ◽  
Mtor Signaling ◽  
Tandem Mass ◽  
Mtor Signaling Pathway ◽  
Apolipoprotein C

Abstract Background: Peritoneal metastasis (PM) occurs frequently in patients with gastric cancer (GC) and confers poor survival. Lipid metabolism and epithelial-mesenchymal transition (EMT) play an important role in GC metastasis. As Apolipoprotein C-II (APOC2) is a key protein in lipid metabolism, few studies have investigated the role of APOC2 in PM. This study aims to elucidate the potential molecular mechanism of APOC2 in the PM of GC.Methods: The Tandem Mass Tagging (TMT) method followed by liquid chromatography-tandem mass spectrometry-based proteomics analysis was used to compare the levels of differentially expressed proteins between human PM and GC tissues. APOC2 expression was evaluated by immunoblotting, and immunohistochemistry analysis (n = 111). APOC2 over-expression and knock-down expression cell models were developed and tested in vitro. RNA sequencing analysis evaluated the changes in gene expression after APOC2 knockdown in GC cells. The Agilent Seahorse XF platform and lipid staining assay were used to evaluate the role of APOC2 in lipid metabolism of GC cells. Spheroid cell invasion assay, apoptosis assay, colony formation assay, wound-healing assays, and transwell assays were performed and peritoneal implants into nude mice were done to assess the biological effects of APOC2. The underlying mechanisms were investigated using Western blot, inhibitor or activator treatment assays.Results: APOC2 was highly abundant in GC cells and PM tissues. And high APOC2 levels in GC tissues correlated with poor patient prognosis. Knockdown of APOC2 inhibited the malignant phenotype of cancer cells and EMT significantly. Massive gene expression alterations after APOC2 knockdown, which were associated with various signaling pathways, especially the PI3K/AKT signaling pathway and lipid metabolism. Furthermore, the regulatory effects of APOC2 on the EMT were partially attributed to the PI3K/AKT/mTOR signaling pathway. The results in vivo also showed that APOC2 modulated GC PM.Conclusions: We verified that knockdown of APOC2 suppressed GC cell Lipid metabolism, proliferation, migration, invasion, and EMT, accompanied by inactivation of PI3K/AKT/mTOR signaling pathway. APOC2 overexpression had the opposite effects GC cell phenotypes and mechanisms. Collectively, our results identified APOC2 in PM as a potential therapeutic target.

scholarly journals Mir-20a-5p Induced WTX Deficiency Promotes Gastric Cancer Progressions Through Regulating PI3K/AKT Signaling Pathway

2020 ◽  
Author(s):  
Jian Li ◽  
Danli Ye ◽  
Peng Shen ◽  
Xiaorong Liu ◽  
Peirong Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Wilms Tumor ◽  
Mtor Signaling ◽  
Luciferase Assay ◽  
Mtor Signaling Pathway ◽  
Pathway Analyses

Abstract Background: The X-linked gene WTX (also called AMER1), has been reported to act as a tumor suppress gene in Wilms tumor. Our previous study reported that WTX expression was significantly reduced in gastric cancer (GC), but the function and mechanism of WTX loss had not been fully elucidated yet. Methods: WTX/miR-20a-5p expression was analyzed in paraffin-embedded archived GC tissues and validated in public databases. KEGG pathway analyses were performed to explore the mechanism of WTX in GC progression. The role of WTX/miR-20a-5p in cell growth, migration, invasion and angiogenesis was investigated in vitro and in vivo. Western blot, immunohistochemistry, RT-PCR, luciferase assay, and Co-immunoprecipitation (Co-IP) were used to detect the regulation of WTX and PI3K/AKT/mTOR signaling by miR-20a-5p.Results: We revealed that WTX served as a tumor suppressor whose loss associated with the aggressive feature of GC by showing hyperproliferation in vitro and high metastasis phenotype in vivo. And WTX expression level was positively correlated with the overall survival of GC patients. Microarray, bioinformatics analysis, and verification experiments showed that WTX loss activated PI3K/AKT/mTOR pathway, and promoted the proliferation and invasion of GC cells. We also discovered that the miR-20a-5P aberrant upregulation was one of the reasons inducing WTX loss in GC which stimulated PI3K phosphorylation to activate PI3K/AKT/mTOR signaling pathway, thus promoted GC progression.Conclusions: This study unveiled the mechanism of GC progression which was, at least partially, caused by miR-20a-5p aberrant upregulation which inhibited WTX expression and thus activate PI3K/AKT/mTOR signaling pathway. It provided a comprehensive understanding of the action of miR-20a-5p/WTX/PI3K/AKT/mTOR signaling pathway in the progression and metastasis of GC.

The PI3K/Akt/mTOR signaling pathway in gastric cancer; from oncogenic variations to the possibilities for pharmacologic interventions

2021 ◽  
pp. 173983
Author(s):  
Ayda Baghery Saghchy Khorasani ◽  
Atieh Pourbagheri-Sigaroodi ◽  
Ali Pirsalehi ◽  
Ava Safaroghli-azar ◽  
Mohammad Reza Zali ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway

scholarly journals ANLN promotes carcinogenesis in oral cancer by regulating the PI3K/mTOR signaling pathway

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Bing Wang ◽  
Xiao-li Zhang ◽  
Chen-xi Li ◽  
Ning-ning Liu ◽  
Min Hu ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Signaling Pathway ◽  
Cell Cycle Progression ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Cell Behaviors ◽  
Rnai Technology ◽  
Tumor Tissues ◽  
Pi3k Signaling Pathway

Abstract Background Oral cancer is a malignant disease that threatenshuman life and greatly reducespatientquality of life. ANLN was reported to promote the progression of cancer. This study aims to investigate the role of ANLNin oral cancer and the underlying molecular mechanism. Methods ANLN expression was downregulated by RNAi technology. The effect of ANLN on cell behaviors, including proliferation, cell cycle progression, invasion, and apoptosis, was detected. Western blotting analysis was used to explore the mechanism by whichANLN functions in oral cancer. Results Data from TCGA database showed that ANLN was expressed at significantly higher levels in tumor tissues thanin normal control tissues. Patients with higher ANLN expression exhibitedshorter survivaltimes. ANLN was alsoabundantly expressedin the cancer cell lines CAL27 and HN30. When ANLN was knocked down in CAL27 and HN30 cells, cell proliferation and colony formation weredecreased. The cell invasion ability was also inhibited. However, the cell apoptosis rate was increased. In addition, the levels of critical members of the PI3K signaling pathway, includingPI3K, mTOR, Akt, and PDK-1, were significantlyreducedafter ANLN was knocked down in CAL27 cells. Conclusions ANLN contributes to oral cancerprogressionand affects activation ofthe PI3K/mTOR signaling pathway. This study providesa new potential targetfor drug development and treatment in oral cancer.

scholarly journals Inhibition of Prostate Cancer DU-145 Cells Proliferation by Anthopleura anjunae Oligopeptide (YVPGP) via PI3K/AKT/mTOR Signaling Pathway

Marine Drugs ◽  
2018 ◽  
Vol 16 (9) ◽  
pp. 325 ◽  
Author(s):  
Xiaojuan Li ◽  
Yunping Tang ◽  
Fangmiao Yu ◽  
Yu Sun ◽  
Fangfang Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Nude Mouse Model ◽  
Dose Dependent

We investigated the antitumor mechanism of Anthopleura anjunae oligopeptide (AAP-H, YVPGP) in prostate cancer DU-145 cells in vitro and in vivo. Results indicated that AAP-H was nontoxic and exhibited antitumor activities. Cell cycle analysis indicated that AAP-H may arrest DU-145 cells in the S phase. The role of the phosphatidylinositol 3-kinase/protein kinase B/mammalian rapamycin target protein (PI3K/AKT/mTOR) signaling pathway in the antitumor mechanism of APP-H was investigated. Results showed that AAP-H treatment led to dose-dependent reduction in the levels of p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448), whereas t-AKT and t-PI3K levels remained unaltered compared to the untreated DU-145 cells. Inhibition of PI3K/AKT/mTOR signaling pathway in the DU-145 cells by employing inhibitor LY294002 (10 μM) or rapamycin (20 nM) effectively attenuated AAP-H-induced phosphorylation of AKT and mTOR. At the same time, inhibitor addition further elevated AAP-H-induced cleaved-caspase-3 levels. Furthermore, the effect of AAP-H on tumor growth and the role of the PI3K/AKT/mTOR signaling pathway in nude mouse model were also investigated. Immunohistochemical analysis showed that activated AKT, PI3K, and mTOR levels were reduced in DU-145 xenografts. Western blotting showed that AAP-H treatment resulted in dose-dependent reduction in p-AKT (Ser473), p-PI3K (p85), and p-mTOR (Ser2448) levels, whereas t-AKT and t-PI3K levels remained unaltered. Similarly, Bcl-xL levels decreased, whereas that of Bax increased after AAP-H treatment. AAP-H also increased initiator (caspase 8 and 9) and executor caspase (caspase 3 and 7) levels. Therefore, the antitumor mechanism of APP-H on DU-145 cells may involve regulation of the PI3K/AKT/mTOR signaling pathway, which eventually promotes apoptosis via mitochondrial and death receptor pathways. Thus, the hydrophobic oligopeptide (YVPGP) can be developed as an adjuvant for the prevention or treatment of prostate cancer in the future.

Celastrol Inhibits the Proliferation and Decreases Drug Resistance of Cisplatin-Resistant Gastric Cancer SGC7901/DDP Cells

2021 ◽  
Vol 21 ◽  
Author(s):  
Dongmei Zhan ◽  
Tengyang Ni ◽  
Haibo Wang ◽  
Mengying Lv ◽  
Masataka Sunagawa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Signaling Pathway ◽  
Resistance Index ◽  
Mtor Signaling ◽  
Control Group ◽  
Human Gastric Cancer ◽  
Cancer Resistance ◽  
Mtor Signaling Pathway ◽  
Expression Levels

Background: This study aimed to determine the effect and mechanism of Celastrol inhibiting the proliferation and decreases drug resistance of cisplatin-resistant gastric cancer cells. Objective: To explore the effect and mechanism of Celastrol on proliferation and drug resistance of human gastric cancer cisplatin-resistant cells SGC7901/DDP. Methods: The thiazole blue (MTT) method was used to detect the sensitivity of human gastric cancer cisplatin-resistant cells SGC7901/DPP to cisplatin and Celastrol to determine the Drug resistance index (DRI). According to the half inhibitory concentration (IC50) value, the action concentration of the following experimental drugs was set to reduce the cytotoxicity; Annexin V-FITC/PI double staining method was used to detect the apoptosis of SGC7901/DDP cells induced by Celastrol; Western Blot was used to examine the expression levels of P-glycoprotein (P-gp), Multidrug Resistance Associated Protein 1 (MRP1), Breast Cancer Resistance Associated Protein (Breast Cancer Resistance)-relative protein (BCRP), and mechanistic Target of Rapamycin (mTOR) pathway related proteins; Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA expression levels of P-gp, MRP1, and BCRP. Results: (1) Compared with the control group (We set the untreated group as the control group), the proliferation of the SGC7901/DPP cells was significantly inhibited after treating with 0.1-6.4μmol/L Celastrol in a time- and concentration-dependent manner (P<0.05). The Drug resistance index DRI of the SGC7901/DPP cells to DDP was 5.64. (2) Compared with the control group, Celastrol could significantly inhibit the proliferation and induce the apoptosis of the SGC7901/DPP cells (P<0.05). (3) The mRNA and protein expression levels of P-gp, MRP1, and BCRP in the SGC7901/DPP cells were significantly higher than those in the SGC7901 cells. However, after treating with Celastrol, the expression levels of P-gp, MRP1, and BCRP in the SGC7901/DPP cells were significantly reduced (P<0.05). (4) Compared with the control group, the Celastrol treatment also reduced the expression of the mTOR signaling pathway related proteins, suggesting that the mTOR signaling pathway may be involved in the process of Celastrol inhibiting the proliferation of the SGC7901/DDP cells and reducing their drug resistance. (5) Significantly, the combination of Celastrol and DDP reduced the expression of P-gp, MRP1, and BCRP in the SGC7901/DPP cells. Conclusion: Celastrol can inhibit the proliferation of the SGC7901/DDP cells, induce their apoptosis, and reduce the expression of drug resistance genes, probably by inhibiting the expression of the proteins related to the mTOR signaling pathway.

Effect of Curcumin on Gene Expression of Trx/TxrR System and PI3K/Akt/mTOR Signaling Pathway in SKOV3 Cells Resistant to Cisplatin

2020 ◽  
Vol 159 ◽  
pp. S55
Author(s):  
Elena Kalinina ◽  
Aseel Ali Hasan ◽  
Albina Petrova ◽  
Maria Novichkova ◽  
Dmitry Zhdanov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Skov3 Cells

scholarly journals CSNK2A1 Promotes Gastric Cancer Invasion Through the PI3K-Akt-mTOR Signaling Pathway

2019 ◽  
Vol Volume 11 ◽  
pp. 10135-10143 ◽  
Author(s):  
Chao Jiang ◽  
Zhenghong Ma ◽  
Guoan Zhang ◽  
Xigui Yang ◽  
Qin Du ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Cancer Invasion ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway

scholarly journals RRS1 Promotes Retinoblastoma Cell Proliferation and Invasion via Activating the AKT/mTOR Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xuejing Yan ◽  
Shen Wu ◽  
Qian Liu ◽  
Jingxue Zhang
Keyword(s):  
Signaling Pathway ◽  
Ribosome Biogenesis ◽  
Regulatory Protein ◽  
Ectopic Expression ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Retinoblastoma Cell ◽  
Cycle Arrest ◽  
Pathway Inhibition

Ribosome biogenesis regulatory protein homolog (RRS1) is a protein required for ribosome biogenesis. Recent studies have identified an oncogenic role of RRS1 in some cancers, whereas the involvement of RRS1 in retinoblastoma (RB) remains to be determined. In this study, we aimed to explore the role of RRS1 in RB. We found that the expression of RRS1 was increased in RB tissues and cells. Lentivirus-mediated RRS1 overexpression promoted the proliferation, growth, and invasion of RB cells. Opposite results were found in RRS1 knockdown cells. In addition, RRS1 silencing induced cell cycle arrest at the G1 phase and apoptosis in RB cells, while RRS1 ectopic expression exhibited the opposite effect. At the molecular level, RRS1 activated the AKT/mTOR signaling pathway, inhibition of which largely blunted the proliferation, growth, and invasion of RB cells. Our study suggests that RRS1 functions as an oncogene in RB through activating the AKT/mTOR signaling pathway.

Sign in / Sign up

Export Citation Format

Share Document