Format

Send to

Choose Destination
Cancer Res. 2012 Dec 15;72(24):6344-50. doi: 10.1158/0008-5472.CAN-12-1068. Epub 2012 Oct 12.

Paracrine Hedgehog signaling drives metabolic changes in hepatocellular carcinoma.

Author information

1
Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.

Abstract

Hepatocellular carcinoma (HCC) typically develops in cirrhosis, a condition characterized by Hedgehog (Hh) pathway activation and accumulation of Hh-responsive myofibroblasts. Although Hh signaling generally regulates stromal-epithelial interactions that support epithelial viability, the role of Hh-dependent myofibroblasts in hepatocarcinogenesis is unknown. Here, we used human HCC samples, a mouse HCC model, and hepatoma cell/myofibroblast cocultures to examine the hypothesis that Hh signaling modulates myofibroblasts' metabolism to generate fuels for neighboring malignant hepatocytes. The results identify a novel paracrine mechanism whereby malignant hepatocytes produce Hh ligands to stimulate glycolysis in neighboring myofibroblasts, resulting in release of myofibroblast-derived lactate that the malignant hepatocytes use as an energy source. This discovery reveals new diagnostic and therapeutic targets that might be exploited to improve the outcomes of cirrhotic patients with HCCs.

PMID:
23066040
PMCID:
PMC3525764
DOI:
10.1158/0008-5472.CAN-12-1068
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center