Targeted disruption of fibrinogen like protein-1 accelerates hepatocellular carcinoma development Academic Article uri icon

Overview

MeSH Major

  • Carcinogenesis
  • Carcinoma, Hepatocellular
  • Fibrinogen
  • Gene Expression Regulation, Neoplastic
  • Liver
  • Liver Neoplasms

abstract

  • Fibrinogen like protein-1 (Fgl1) is a predominantly liver expressed protein that has been implicated as both a hepatoprotectant and a hepatocyte mitogen. Fgl1 expression is decreased in hepatocellular carcinoma (HCC) and its loss correlates with a poorly differentiated phenotype. To better elucidate the role of Fgl1 in hepatocarcinogenesis, we treated mice wild type or null for Fgl1 with diethyl nitrosamine and monitored for incidence of hepatocellular cancer. We find that mice lacking Fgl1 develop HCC at more than twice the rate of wild type mice. We show that hepatocellular cancers from Fgl1 null mice are molecularly distinct from those of the wild type mice. In tumors from Fgl1 null mice there is enhanced activation of Akt and downstream targets of the mammalian target of rapamycin (mTOR). In addition, there is paradoxical up regulation of putative hepatocellular cancer tumor suppressors; tripartite motif-containing protein 35 (Trim35) and tumor necrosis factor super family 10b (Tnfrsf10b). Taken together, these findings suggest that Fgl1 acts as a tumor suppressor in hepatocellular cancer through an Akt dependent mechanism and supports its role as a potential therapeutic target in HCC.

publication date

  • June 30, 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4594872

Digital Object Identifier (DOI)

  • 10.1016/j.bbrc.2015.07.078

PubMed ID

  • 26225745

Additional Document Info

start page

  • 167

end page

  • 73

volume

  • 465

number

  • 2