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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3480444?pdf=render |
| _version_ | 1818587539929300992 |
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| author | Yanli Ma Qingbin Kong Hui Hua Ting Luo Yangfu Jiang |
| author_facet | Yanli Ma Qingbin Kong Hui Hua Ting Luo Yangfu Jiang |
| author_sort | Yanli Ma |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T09:10:28Z |
| format | Article |
| id | doaj.art-6e720198f7c449bdba87b67bc0158bc9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T09:10:28Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6e720198f7c449bdba87b67bc0158bc92022-12-21T22:37:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01710e4796110.1371/journal.pone.0047961Aflatoxin B1 up-regulates insulin receptor substrate 2 and stimulates hepatoma cell migration.Yanli MaQingbin KongHui HuaTing LuoYangfu JiangAflatoxin 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.http://europepmc.org/articles/PMC3480444?pdf=render |
| spellingShingle | Yanli Ma Qingbin Kong Hui Hua Ting Luo Yangfu Jiang Aflatoxin B1 up-regulates insulin receptor substrate 2 and stimulates hepatoma cell migration. PLoS ONE |
| title | Aflatoxin B1 up-regulates insulin receptor substrate 2 and stimulates hepatoma cell migration. |
| title_full | Aflatoxin B1 up-regulates insulin receptor substrate 2 and stimulates hepatoma cell migration. |
| title_fullStr | Aflatoxin B1 up-regulates insulin receptor substrate 2 and stimulates hepatoma cell migration. |
| title_full_unstemmed | Aflatoxin B1 up-regulates insulin receptor substrate 2 and stimulates hepatoma cell migration. |
| title_short | Aflatoxin B1 up-regulates insulin receptor substrate 2 and stimulates hepatoma cell migration. |
| title_sort | aflatoxin b1 up regulates insulin receptor substrate 2 and stimulates hepatoma cell migration |
| url | http://europepmc.org/articles/PMC3480444?pdf=render |
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