Aflatoxin B1 up-regulates insulin receptor substrate 2 and stimulates hepatoma cell migration

Aflatoxin B1 (AFB1) is a potent carcinogen that can induce hepatocellular carcinoma. AFB1-8,9-exo-epoxide, one of AFB1 metabolites, acts as a mutagen to react with DNA and induce gene mutations, including the tumor suppressor p53. In addition, AFB1 reportedly stimulates IGF receptor activation. Aber...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2012-10, Vol.7 (10), p.e47961
Main Authors: Ma, Yanli, Kong, Qingbin, Hua, Hui, Luo, Ting, Jiang, Yangfu
Format: Article
Language:English
Subjects:
Aberration
Activation
Aflatoxin B1
Aflatoxin B1 - metabolism
AKT protein
Biology
Carcinogens
Carcinogens - metabolism
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - pathology
Cell Line
Cell migration
Cell Movement
Deoxyribonucleic acid
Development and progression
DNA
Gene mutation
Genetic aspects
Hep G2 Cells
Hepatocellular carcinoma
Hepatocytes
Hepatoma
Humans
Inhibitors
Insulin
Insulin Receptor Substrate Proteins - metabolism
Insulin-like growth factor I
Insulin-like growth factors
Iridium
Kinases
Leukocyte migration
Liver
Liver - cytology
Liver - metabolism
Liver - pathology
Liver cancer
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Medicine
Metabolites
Mutation
p53 Protein
Phosphorylation
Proteasomes
Receptor mechanisms
Receptor, IGF Type 1 - metabolism
Signal Transduction
Signaling
Substrates
Tumor proteins
Tumor suppressor genes
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Aflatoxin B1 (AFB1) is a potent carcinogen that can induce hepatocellular carcinoma. AFB1-8,9-exo-epoxide, one of AFB1 metabolites, acts as a mutagen to react with DNA and induce gene mutations, including the tumor suppressor p53. In addition, AFB1 reportedly stimulates IGF receptor activation. Aberrant activation of IGF-I receptor (IGF-IR) signaling is tightly associated with various types of human tumors. In the current study, we investigated the effects of AFB1 on key elements in IGF-IR signaling pathway, and the effects of AFB1 on hepatoma cell migration. The results demonstrated that AFB1 induced IGF-IR, Akt, and Erk1/2 phosphorylation in hepatoma cell lines HepG2 and SMMC-7721, and an immortalized human liver cell line Chang liver. AFB1 also down-regulated insulin receptor substrate (IRS) 1 but paradoxically up-regulated IRS2 through preventing proteasomal degradation. Treatment of hepatoma cells and Chang liver cells with IGF-IR inhibitor abrogated AFB1-induced Akt and Erk1/2 phosphorylation. In addition, IRS2 knockdown suppressed AFB1-induced Akt and Erk1/2 phosphorylation. Finally, AFB1 stimulated hepatoma cell migration. IGF-IR inhibitor or IRS2 knockdown suppressed AFB1-induced hepatoma cell migration. These data demonstrate that AFB1 stimulates hepatoma cell migration through IGF-IR/IRS2 axis.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0047961