The Role of AMPK in Metabolic Changes in Pancreatic Cancer Cells through High Protein Diet

Even though the tumour suppressive role of PTEN is well-known, its prognostic implications are ambiguous. The objective of this study was to further explore the function of PTEN expression in human pancreatic cancer. The expression of PTEN has been dominant in various human cancers including pancreatic cancer when compared with their matched normal tissues. The pancreatic cancer cells have been divided into PTEN blockade-susceptible and PTEN blockade-impassible groups dependent on targeting PTEN by altering intracellular signaling. The expression of PTEN has led to varying clinical outcomes of pancreatic cancer based on GEO Series (GSE) data analysis and Liptak’s z analysis. Differential dependency to PTEN blockade has been ascertained based on the expression of polo-like kinase1 PLK1 in pancreatic cancer cells. The prognostic value of PTEN also depends on PLK1 expression in pancreatic cancer. Collectively, the present study provides a rationale for targeting PTEN as a promising therapeutic strategy dependent on PLK1 expressions using a companion biomarker discovery platform.

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Potential role of IGF-1 in parathyroid hormone-related renal growth induced by high protein diet in uninephrectomized rats

Kidney International ◽

10.1038/ki.1995.263 ◽

1995 ◽

Vol 48 (1) ◽

pp. 33-38 ◽

Cited By ~ 6

Author(s):

Joseph Caverzasio ◽

T. Shigematsu ◽

R. Rizzoli ◽

Jean-Philippe Bonjour

Keyword(s):

Parathyroid Hormone ◽

Potential Role ◽

High Protein Diet ◽

High Protein ◽

Protein Diet ◽

Renal Growth

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Hypoxia-induced shedding of MICA and HIF1A-mediated immune escape of pancreatic cancer cells from NK cells: role of circ_0000977/miR-153 axis

RNA Biology ◽

10.1080/15476286.2019.1649585 ◽

2019 ◽

Vol 16 (11) ◽

pp. 1592-1603 ◽

Cited By ~ 22

Author(s):

Zheng-Lin Ou ◽

Zhen Luo ◽

Wei Wei ◽

Shuai Liang ◽

Tai-Long Gao ◽

...

Keyword(s):

Pancreatic Cancer ◽

Nk Cells ◽

Cancer Cells ◽

Immune Escape ◽

Pancreatic Cancer Cells

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Characterization of homocysteine metabolism in the rat liver

Biochemical Journal ◽

10.1042/bj3500685 ◽

2000 ◽

Vol 350 (3) ◽

pp. 685-692 ◽

Cited By ~ 43

Author(s):

Lori M. STEAD ◽

Margaret E. BROSNAN ◽

John T. BROSNAN

Keyword(s):

Amino Acid ◽

Dietary Protein ◽

High Protein Diet ◽

Plasma Homocysteine ◽

High Protein ◽

Protein Diet ◽

Total Plasma ◽

Methionine Concentration ◽

Protein Group

Recent evidence suggests that an increased plasma concentration of the sulphur amino acid homocysteine is a risk factor for the development of vascular disease. The tissue(s) responsible for homocysteine production and export to the plasma are not well known. However, given the central role of the liver in amino acid metabolism, we developed a rat primary hepatocyte model in which homocysteine (and cysteine) production and export were examined. The dependence of homocysteine export from incubated hepatocytes on methionine concentration fitted well to a rectangular hyperbola, with half-maximal homocysteine export achieved at methionine concentrations of approx. 0.44mM. Hepatocytes incubated with 1mM methionine and 1mM serine (a substrate for the transulphuration pathway of homocysteine removal) produced and exported significantly less homocysteine (25–40%) compared with cells incubated with 1mM methionine alone. The effects of dietary protein on homocysteine metabolism were also examined. Rats fed a 60% protein diet had a significantly increased total plasma homocysteine level compared with rats fed a 20% protein diet. Invitro effects of dietary protein were examined using hepatocytes isolated from animals maintained on these diets. When incubated with 1mM methionine, hepatocytes from rats fed the high protein diet exported significantly more homocysteine compared with hepatocytes from rats fed the normal protein diet. Inclusion of serine significantly lowered homocysteine export in the normal protein group, but the effect was more marked in the high protein group. Invivo effects of serine were also examined. Rats fed a high protein diet enriched with serine had significantly lower total plasma homocysteine (25–30%) compared with controls. These data indicate a significant role for the liver in the regulation of plasma homocysteine levels.

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Linc-DYNC2H1-4 promotes EMT and CSC phenotypes by acting as a sponge of miR-145 in pancreatic cancer cells

Cell Death and Disease ◽

10.1038/cddis.2017.311 ◽

2017 ◽

Vol 8 (7) ◽

pp. e2924-e2924 ◽

Cited By ~ 23

Author(s):

Yuran Gao ◽

Zhicheng Zhang ◽

Kai Li ◽

Liying Gong ◽

Qingzhu Yang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

Ectopic Expression ◽

Pancreatic Cancer Cell Line ◽

Mesenchymal Transition ◽

Gemcitabine Resistance ◽

Pancreatic Cancer Cells ◽

Sense Strand ◽

The Impact

AbstractThe acquisition of epithelial–mesenchymal transition (EMT) and/or existence of a sub-population of cancer stem-like cells (CSC) are associated with malignant behavior and chemoresistance. To identify which factor could promote EMT and CSC formation and uncover the mechanistic role of such factor is important for novel and targeted therapies. In the present study, we found that the long intergenic non-coding RNA linc-DYNC2H1-4 was upregulated in pancreatic cancer cell line BxPC-3-Gem with acquired gemcitabine resistance. Knockdown of linc-DYNC2H1-4 decreased the invasive behavior of BxPC-3-Gem cells while ectopic expression of linc-DYNC2H1-4 promoted the acquisition of EMT and stemness of the parental sensitive cells. Linc-DYNC2H1-4 upregulated ZEB1, the EMT key player, which led to upregulation and downregulation of its targets vimentin and E-cadherin respectively, as well as enhanced the expressions of CSC makers Lin28, Nanog, Sox2 and Oct4. Linc-DYNC2H1-4 is mainly located in the cytosol. Mechanically, it could sponge miR-145 that targetsZEB1,Lin28,Nanog,Sox2,Oct4to restore these EMT and CSC-associated genes expressions. We proved thatMMP3, the nearby gene of linc-DYNC2H1-4 in the sense strand, was also a target of miR-145. Downregulation ofMMP3by miR-145 was reverted by linc-DYNC2H1-4, indicating that competing with miR-145 is one of the mechanisms for linc-DYNC2H1-4 to regulateMMP3. In summary, our results explore the important role of linc-DYNC2H1-4 in the acquisition of EMT and CSC, and the impact it has on gemcitabine resistance in pancreatic cancer cells.

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