Impaired endogenous activation of peroxisome proliferator activated receptor (PPAR)α by human colon cancers

2001 ◽  
Vol 120 (5) ◽  
pp. A505-A505
Author(s):  
L JACKSON ◽  
A BENNETT ◽  
C HAWKEY
Keyword(s):  
Human Colon ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Colon Cancers

scholarly journals AMPK Promotes Aberrant PGC1β Expression To Support Human Colon Tumor Cell Survival

2015 ◽  
Vol 35 (22) ◽  
pp. 3866-3879 ◽  
Author(s):  
Kurt W. Fisher ◽  
Binita Das ◽  
Hyun Seok Kim ◽  
Beth K. Clymer ◽  
Drew Gehring ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Survival ◽  
Human Colon ◽  
Colon Tumor ◽  
Peroxisome Proliferator ◽  
Specific Expression ◽  
Peroxisome Proliferator Activated Receptor ◽  
Tumor Cell Survival ◽  
Kinase Suppressor Of Ras ◽  
Colon Tumor Cell

A major goal of cancer research is the identification of tumor-specific vulnerabilities that can be exploited for the development of therapies that are selectively toxic to the tumor. We show here that the transcriptional coactivators peroxisome proliferator-activated receptor gamma coactivator 1β (PGC1β) and estrogen-related receptor α (ERRα) are aberrantly expressed in human colon cell lines and tumors. With kinase suppressor of Ras 1 (KSR1) depletion as a reference standard, we usedfunctionalsignatureontology (FUSION) analysis to identify the γ1 subunit of AMP-activated protein kinase (AMPK) as an essential contributor to PGC1β expression and colon tumor cell survival. Subsequent analysis revealed that a subunit composition of AMPK (α2β2γ1) is preferred for colorectal cancer cell survival, at least in part, by stabilizing the tumor-specific expression of PGC1β. In contrast, PGC1β and ERRα are not detectable in nontransformed human colon epithelial cells, and depletion of the AMPKγ1 subunit has no effect on their viability. These data indicate that Ras oncogenesis relies on the aberrant activation of a PGC1β-dependent transcriptional pathway via a specific AMPK isoform.

scholarly journals Vitamin D3 promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of β-catenin signaling

2001 ◽  
Vol 154 (2) ◽  
pp. 369-388 ◽  
Author(s):  
Héctor G. Pálmer ◽  
José Manuel González-Sancho ◽  
Jesús Espada ◽  
María T. Berciano ◽  
Isabel Puig ◽  
...  
Keyword(s):  
Colon Carcinoma ◽  
Vitamin D3 ◽  
Target Genes ◽  
Human Colon ◽  
Carcinoma Cells ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Vitamin D Receptors ◽  
Colon Carcinoma Cells ◽  
E Cadherin

The β-catenin signaling pathway is deregulated in nearly all colon cancers. Nonhypercalcemic vitamin D3 (1α,25-dehydroxyvitamin D3) analogues are candidate drugs to treat this neoplasia. We show that these compounds promote the differentiation of human colon carcinoma SW480 cells expressing vitamin D receptors (VDRs) (SW480-ADH) but not that of a malignant subline (SW480-R) or metastasic derivative (SW620) cells lacking VDR. 1α,25(OH)2D3 induced the expression of E-cadherin and other adhesion proteins (occludin, Zonula occludens [ZO]-1, ZO-2, vinculin) and promoted the translocation of β-catenin, plakoglobin, and ZO-1 from the nucleus to the plasma membrane. Ligand-activated VDR competed with T cell transcription factor (TCF)-4 for β-catenin binding. Accordingly, 1α,25(OH)2D3 repressed β-catenin–TCF-4 transcriptional activity. Moreover, VDR activity was enhanced by ectopic β-catenin and reduced by TCF-4. Also, 1α,25(OH)2D3 inhibited expression of β-catenin–TCF-4-responsive genes, c-myc, peroxisome proliferator-activated receptor δ, Tcf-1, and CD44, whereas it induced expression of ZO-1. Our results show that 1α,25(OH)2D3 induces E-cadherin and modulates β-catenin–TCF-4 target genes in a manner opposite to that of β-catenin, promoting the differentiation of colon carcinoma cells.

scholarly journals Serine Palmitoyltransferase Controls Stemness of Intestinal Progenitors

2020 ◽  
Author(s):  
Ying Li ◽  
Bhagirath Chaurasia ◽  
Vincent Kaddai ◽  
Joseph L. Wilkerson ◽  
J. Alan Maschek ◽  
...  
Keyword(s):  
Stem Cell ◽  
Fatty Acid ◽  
Human Colon ◽  
Intestinal Stem Cell ◽  
Peroxisome Proliferator ◽  
Acid Uptake ◽  
Serine Palmitoyltransferase ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding ◽  
Epithelial Regeneration

SummaryCancers of the gastrointestinal tract including esophageal adenocarcinomas, colorectal cancers, and cancers of the gastric cardia are common comorbidities of obesity. Excessive delivery of macronutrients to the cells lining the gut can increase one’s risk for these cancer by inducing imbalances in the rate of intestinal stem cell proliferation vs. differentiation, which can produce polyps and other aberrant growths. We demonstrate that serine palmitoyltransferase (SPT), which diverts dietary fatty and amino acids into the sphingolipid biosynthesis pathway, is a critical modulator of intestinal stem cell homeostasis. SPT and other enzymes in the biosynthetic pathway are upregulated in human colon tumors. These enzymes produce sphingolipids that serve as pro-stemness signals that stimulate peroxisome-proliferator activated receptor alpha (PPARα)-mediated induction of fatty acid binding protein-1. This increases fatty acid uptake and oxidation and enhances the stemness program. Serine palmitoyltransferase thus serves as a critical link between dietary macronutrients, epithelial regeneration, and cancer risk.

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