51. Mesothelin Activates Akt Signaling Pathway Which Leads To NF-κB Activation and Resistance To TNF-α Induced Apoptosis in Pancreatic Cancer Cells

Abstract Background Pancreatic cancer is one of the most serious digestive malignancies. At present, there is an extreme lack of effective strategies in clinical treatment. The purpose of this study is to identify key genes and pathways in the development of pancreatic cancer and provide targets for the treatment of pancreatic cancer. Methods GSE15471 and GSE62165 were used to screen differentially expressed genes by GEO2R tool. Hub genes prognostic potential assessed using the GEPIA and Kaplan–Meier plotter databases. The drug susceptibility data of pan-cancer cell lines is provided by The Genomics of Drug Sensitivity in Cancer Project (GDSC). Finally, the effects of PI3K–Akt signaling pathway inhibitors on cell viability of pancreatic cancer cells were detected by cell proliferation and invasion assays. Results A total of 609 differentially expressed genes were screened and enriched in the focal adhesion, phagosome and PI3K–Akt signaling pathway. Of the 15 hub genes we found, four were primarily associated with the PI3K–Akt signaling pathway, including COL3A1, EGF, FN1 and ITGA2. GDSC analysis showed that mTOR inhibitors are very sensitive to pancreatic cancer cells with mutations in EWSR1.FLI1 and RNF43. Cell proliferation and invasion results showed that mTOR inhibitors (GSK2126458) can inhibit the proliferation of pancreatic cancer cells. Conclusions This study suggested that the PI3K–Akt signaling pathway may be a key pathway for pancreatic cancer, our study uncovered the potential therapeutic potential of GSK2126458, a specific mTOR inhibitor, for pancreatic cancer.

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Inhibition of PI3K/AKT Signaling Pathway Radiosensitizes Pancreatic Cancer Cells with ARID1A Deficiency in Vitro

Journal of Cancer ◽

10.7150/jca.21306 ◽

2018 ◽

Vol 9 (5) ◽

pp. 890-900 ◽

Cited By ~ 10

Author(s):

Lin Yang ◽

Guanghai Yang ◽

Yingjun Ding ◽

Yuhong Dai ◽

Sanpeng Xu ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Pancreatic Cancer Cells

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Novel semi-synthetic Cu (II)-cardamonin complex exerts potent anticancer activity against triple negative breast and pancreatic cancer cells via inhibition of the Akt signaling pathway

10.21203/rs.3.rs-225415/v1 ◽

2021 ◽

Author(s):

Md Shahadat Hossan ◽

Mohammed Khaled Bin Break ◽

Tracey D. Bradshaw ◽

Hilary M. Collins ◽

Christophe Wiart ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Triple Negative ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Microtubule Network ◽

Pancreatic Cancer Cells ◽

M Phase ◽

Network Disruption

Abstract Triple negative breast cancer (TNBC) and pancreatic cancer are two of the most aggressive types of cancer that lack effective treatments. We have previously reported the semi-synthesis of a novel Cu (II)-cardamonin complex (19) that demonstrated potent anti-tumour activity. In this study, we further investigated the bioactivity and mode of action of 19 against MDA-MB-468 and PANC-1 cancer cells in an attempt to discover an effective anticancer agent for TNBC and pancreatic cancer, respectively. Results revealed that 19 abolished formation of MDA-MB-468 and PANC-1 colonies, exerted growth inhibitory activity and inhibited the migration of cancer cells. Further mechanistic studies showed that it induced DNA damage resulting in G2/M-phase arrest and microtubule network disruption. Moreover, there was an increase in ROS production which may have contributed to the observed induction of apoptosis, corroborated by activation of caspase-3/7, cleavage of PARP and downregulation of Mcl-1. Complex 19 also decreased the expression levels of p-Akt and p-4EBP1 in both cell lines, which indicates that the compound exerted its activity, at least in part, via inhibition of the Akt signaling pathway. Furthermore, it decreased the expression of c-Myc in PANC-1 cells only which suggests that it may exert its bioactivity via multiple mechanisms of action pertinent to tumourigenesis. These results demonstrate the potential of 19 as a promising therapeutic agent for TNBC and pancreatic cancer.

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ERas regulates cell proliferation and epithelial–mesenchymal transition by affecting Erk/Akt signaling pathway in pancreatic cancer

Human Cell ◽

10.1007/s13577-020-00401-2 ◽

2020 ◽

Vol 33 (4) ◽

pp. 1186-1196

Author(s):

Yang Liu ◽

Peng Qin ◽

Rong Wu ◽

Lianfang Du ◽

Fan Li

Keyword(s):

Pancreatic Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Signaling Pathway ◽

Colony Formation ◽

Epithelial Mesenchymal Transition ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Mesenchymal Transition ◽

Pancreatic Cancer Cells

Abstract Pancreatic cancer is the fourth most common lethal malignancy with an overall 5-year survival rate of less than 5%. ERas, a novel Ras family member, was first identified in murine embryonic stem cells and is upregulated in various cancers. However, the expression and potential role of ERas in pancreatic cancer have not been investigated. In this study, we found that ERas mRNA and protein were upregulated in pancreatic cancer tissues and cells compared with controls. Knockdown of ERas in pancreatic cancer cells by siRNA significantly decreased cell proliferation, colony formation, migration, and invasion and promoted cell apoptosis in vitro. Epithelial–mesenchymal transition (EMT) is closely related to tumor progression. We observed a significant decrease in N-cadherin expression in pancreatic cancer cells in response to ERas gene silencing by immunofluorescence assay and western blot. Furthermore, tumor growth and EMT were inhibited in xenografts derived from pancreatic cancer cells with ERas downregulation. We further investigated the regulatory mechanisms of ERas in pancreatic cancer and found that ERas may activate the Erk/Akt signaling pathway. Moreover, Erk inhibitor decreased pancreatic cancer cells proliferation and colony formation activities. Our data suggest that targeting ERas and its relevant signaling pathways might represent a novel therapeutic approach for the treatment of pancreatic cancer.

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