github link
Accession IconGSE55587

Metabolic reprogramming of stromal fibroblasts through p62-mTORC1 signaling promotes inflammation and tumorigenesis

Organism Icon Mus musculus
Sample Icon 12 Downloadable Samples
Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Submitter Supplied Information

Description
The tumor microenvironment plays a critical role in cancer progression, but the precise mechanisms by which stromal cells influence the tumor epithelium are poorly understood. The signaling adapter p62 has been implicated as a positive regulator of epithelial tumorigenesis; however, its role in the stroma is unknown. We show here that p62 levels are reduced in the stroma of several tumors. Also, orthotopic and organotypic studies demonstrate that the loss of p62 in the tumor microenvironment or stromal fibroblasts resulted in increased tumorigenesis of epithelial prostate cancer cells. The mechanism involves the regulation of cellular redox through an mTORC1/c-Myc pathway of stromal glucose and amino acid metabolism. Inhibition of the pathway by p62 deficiency results in increased stromal IL-6 production, which is required for tumor promotion in the epithelial compartment. Thus, p62 is an anti-inflammatory tumor suppressor that acts through modulation of metabolism in the tumor stroma.
PubMed ID
Total Samples
12
Submitter’s Institution

Samples

Show of 0 Total Samples
Filter
Add/Remove
Accession Code
Title
Specimen part
Processing Information
Additional Metadata
No rows found
Loading...