scholarly journals NOX4: a potential therapeutic target for pancreatic cancer and its mechanism

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yawei Bi ◽  
Xiao Lei ◽  
Ningli Chai ◽  
Enqiang Linghu
Keyword(s):  
Pancreatic Cancer ◽  
Therapeutic Target ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Human Pancreatic Cancer ◽  
Cancer Tissue ◽  
Pancreatic Cancer Tissue ◽  
Potential Therapeutic Target ◽  
Nadph Oxidase 4 ◽  
Cancer Occurrence ◽  
Nox Family

AbstractNicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) is one of the seven isoforms of NOX family, which is upregulated in pancreatic cancer cell, mouse model of pancreatic cancer and human pancreatic cancer tissue. NOX4 is a constitutively active enzyme that primarily produces hydrogen peroxide, which exhibits completely different properties from other subtypes of NOX family. More importantly, recent studies illuminate that NOX4 promotes pancreatic cancer occurrence and development in different ways. This review summarizes the potential roles and its mechanism of NOX4 in pancreatic cancer and explores NOX4 as the potential therapeutic target in pancreatic cancer.

scholarly journals Identification of phosphoenolpyruvate carboxykinase 1 as a potential therapeutic target for pancreatic cancer

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Xiao-ren Zhu ◽  
Shi-qing Peng ◽  
Le Wang ◽  
Xiao-yu Chen ◽  
Chun-xia Feng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Therapeutic Target ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Human Pancreatic Cancer ◽  
Migration And Invasion ◽  
Potential Therapeutic Target ◽  
Protein Levels ◽  
Pancreatic Cancer Cells

AbstractPancreatic cancer is the third leading cause of cancer-related mortalities and is characterized by rapid disease progression. Identification of novel therapeutic targets for this devastating disease is important. Phosphoenolpyruvate carboxykinase 1 (PCK1) is the rate-limiting enzyme of gluconeogenesis. The current study tested the expression and potential functions of PCK1 in pancreatic cancer. We show that PCK1 mRNA and protein levels are significantly elevated in human pancreatic cancer tissues and cells. In established and primary pancreatic cancer cells, PCK1 silencing (by shRNA) or CRISPR/Cas9-induced PCK1 knockout potently inhibited cell growth, proliferation, migration and invasion, and induced robust apoptosis activation. Conversely, ectopic overexpression of PCK1 in pancreatic cancer cells accelerated cell proliferation and migration. RNA-seq analyzing of differentially expressed genes (DEGs) in PCK1-silenced pancreatic cancer cells implied that DEGs were enriched in the PI3K-Akt-mTOR cascade. In pancreatic cancer cells, Akt-mTOR activation was largely inhibited by PCK1 shRNA, but was augmented after ectopic PCK1 overexpression. In vivo, the growth of PCK1 shRNA-bearing PANC-1 xenografts was largely inhibited in nude mice. Akt-mTOR activation was suppressed in PCK1 shRNA-expressing PANC-1 xenograft tissues. Collectively, PCK1 is a potential therapeutic target for pancreatic cancer.

scholarly journals Ex-vivo evaluation of gene therapy vectors in human pancreatic (cancer) tissue slices

2009 ◽  
Vol 15 (11) ◽  
pp. 1359 ◽  
Author(s):  
Michael A van Geer ◽  
Koert FD Kuhlmann ◽  
Conny T Bakker ◽  
Fibo JW ten Kate ◽  
Ronald PJ Oude Elferink ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Gene Therapy ◽  
Ex Vivo ◽  
Human Pancreatic Cancer ◽  
Cancer Tissue ◽  
Tissue Slices ◽  
Pancreatic Cancer Tissue ◽  
Gene Therapy Vectors

scholarly journals TSPAN1 promotes human pancreatic cancer cells proliferation by modulating CDK1 via Akt

2020 ◽  
Author(s):  
Xin Wang ◽  
Xiaozhuo Gao ◽  
Jiaxun Tian ◽  
Rui Zhang ◽  
Yun Qiao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Therapeutic Target ◽  
Human Pancreatic Cancer ◽  
Potential Therapeutic Target ◽  
Qrt Pcr ◽  
Pancreatic Cancers ◽  
Pancreatic Cancer Cells ◽  
M Phase

AbstractBackgroundTo explore the potential therapeutic target to treat pancreatic cancers, Tspan1 was detected in human pancreatic cancer tissue and human pancreatic ductal adenocarcinoma cells and functional role of Tspan1 on proliferation was explored and the mechanism was investigated.Materials and MethodsTspan1 in PCC tissue and PDAC cell lines was measured by qRT-PCR and Western blot. Tspan1 was knock-downed and over-expressed in cells via transfection with Tspan1-siRNA and pLNCX-TSPAN1-cDNA, cell survival, proliferation and cell cycle were measured with MTT, Alamar blue and Flow Cytometry assay. The mRNA and protein expression were assessed by qRT-PCR and Western blotting. The expression of PI3K, Akt and p-Akt were detected, and CDK1 siRNA and specific inhibitor of Akt were used to explore the mechanism of TSPAN1 promoting PDAC cells proliferation.ResultsTspan1 expression in PCC tissue and PDAC cells was increased. Transfection of siRNA targeting Tspan1 in BxPC3 and PNAC-1 cells obviously decreased cell proliferation and down-regulated CDK1 expression. Consistently, both cell proliferation and CDK1 expression in BxPC3 and PNAC-1 cells were up-regulated with pLNCX-TSPAN1-cDNA transfection. Cell cycle analysis showed that after knockdown of Tspan1 the G2/M phase ratio was increased to cause mitosis arrest, and TSPAN1 overexpression caused cell cycle transition from G2 to M phase to promote cell proliferation. And these were dependent on the modulation of CDK1 expression via Akt.ConclusionTspan1 up-regulates CDK1 expression via activating Akt to promote human PCC cell proliferation and silencing of Tspan1 may be a potential therapeutic target to treat pancreatic cancers.

Association between Expression Levels of CA 19-9 and N-Acetylglucosamine-β1,3-Galactosyltransferase 5 Gene in Human Pancreatic Cancer Tissue

Pathobiology ◽  
2004 ◽  
Vol 71 (1) ◽  
pp. 26-34 ◽  
Author(s):  
Nobuyasu Hayashi ◽  
Shoji Nakamori ◽  
Jiro Okami ◽  
Hiroaki Nagano ◽  
Keizo Dono ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Human Pancreatic Cancer ◽  
Cancer Tissue ◽  
Pancreatic Cancer Tissue ◽  
Expression Levels ◽  
I Gene

scholarly journals Multimodal Treatment Eliminates Cancer Stem Cells and Leads to Long-Term Survival in Primary Human Pancreatic Cancer Tissue Xenografts

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e66371 ◽  
Author(s):  
Patrick C. Hermann ◽  
Sara M. Trabulo ◽  
Bruno Sainz ◽  
Anamaria Balic ◽  
Elena Garcia ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Multimodal Treatment ◽  
Human Pancreatic Cancer ◽  
Cancer Tissue ◽  
Pancreatic Cancer Tissue ◽  
Term Survival ◽  
Long Term Survival

scholarly journals YOD1 Serves as a Potential Prognostic Biomarker For Pancreatic Cancer

2021 ◽  
Author(s):  
Zhishuo Zhang ◽  
Wenxia Zhao ◽  
Yiming Li ◽  
Yang Li ◽  
Yang Liu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Expression Level ◽  
Human Pancreatic Cancer ◽  
Cancer Tissue ◽  
Post Translational Modification ◽  
Pancreatic Cancer Cells ◽  
Proliferation And Metastasis ◽  
Cancer Tissues

Abstract Background Ubiquitination is a basic post-translational modification of intracellular proteins and can be reversed enzymatically by DUBs (deubiquitinating enzymes). More than 90 DUBs have been identified. Among them, the deubiquitinating enzyme YOD1, a member of the ovarian tumor domain protease (OTUs) subfamily, is involved in the regulation of endoplasmic reticulum (ER)-related degradation pathways. In fact, it is reported that YOD1 is an important proliferation and metastasis-inducing gene, which can stimulate the characteristics of cancer stem cells and maintain circulating tumor cells (CTC). However, the expression level, prognostic effect, biological function and mechanism of YOD1 in pancreatic cancer are still unclear. ResultsIn the GEO and TCGA databases, YOD1 mRNA expression is significantly up-regulated in a variety of human pancreatic cancer tissues. Survival analysis showed that the up-regulation of YOD1 can predict poor prognosis of pancreatic cancer. Cox analysis showed that high YOD1 expression is an independent prognostic factor of pancreatic cancer. ROC analysis shows that YOD1 has significant diagnostic value. The immunohistochemistry (IHC) results showed that the protein expression level of YOD1 in pancreatic cancer tissue was higher than that in neighboring non-pancreatic cancer tissues (P<0.001). In addition, we found that YOD1 expression is negatively correlated with the infiltration level of CD8+ T cells, macrophages, neutrophils and dendritic cells (DC) in pancreatic cancer. The expression of YOD1 has a strong correlation with the different immune marker sets in PAAD. Co-expression network and functional enrichment analysis indicate that YOD1 may participate in the development of pancreatic cancer through cell adhesion molecules, p53, Hippo, TGF-β and other pathways. The experimental results of EDU, Transwell and Western blot indicate that YOD1 is highly expressed in pancreatic cancer cells and pancreatic cancer tissues, and its overexpression can promote the proliferation and metastasis of pancreatic cancer cells.Conclusion Our results indicate that YOD1 may be a useful biomarker for the prognosis of human pancreatic cancer, and it may also be a potential molecular target for the diagnosis and treatment of pancreatic cancer.

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