Transcriptomics

Dataset Information

0

Cholesterol pathway inhibition induces TGFβ signaling to promote basal differentiation in pancreatic cancer


ABSTRACT: Oncogenic transformation alters the metabolism of cellular lipids to sustain tumor growth. We define a reciprocal mechanism by which cholesterol metabolism controls the formation and differentiation of pancreatic ductal adenocarcinoma (PDAC). Disruption of distal cholesterol biosynthesis by conditional inactivation of Nsdhl, or treatment with cholesterol-lowering statins caused murine pancreatic carcinomas induced by KrasG12D expression and homozygous Trp53 loss to undergo a differentiation switch from a glandular to basal (mesenchymal) phenotype. In parallel, PDACs from patients receiving statins had enhanced mesenchymal features. Mechanistically, statins and NSDHL loss induced sterol response element binding protein 1 (SREBP1), promoting autocrine transforming growth factor beta (TGF) signaling, inducing epithelial-mesenchymal transition. Activation of promesenchymal TGFβ effectors by cholesterol-lowering statins may select for poorly differentiated carcinomas.

ORGANISM(S): Mus musculus

PROVIDER: GSE156210 | GEO | 2020/08/14

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2020-04-30 | GSE149566 | GEO
2007-04-26 | GSE6877 | GEO
2023-05-31 | GSE176531 | GEO
2017-12-30 | E-MTAB-3979 | biostudies-arrayexpress
| 2079365 | ecrin-mdr-crc
2011-09-04 | E-GEOD-24187 | biostudies-arrayexpress
2011-09-05 | GSE24187 | GEO
2011-09-05 | GSE24186 | GEO
2024-06-27 | GSE252127 | GEO
| PRJNA9561 | ENA