title: Aflatoxin B1 induces Src phosphorylation and stimulates lung cancer cell migration.
abstract: AflatoxinB1 (AFB1) is well known as a potent carcinogen. Epidemiological studies have shown an association between AFB1 exposure and lung cancer in humans. AFB1 can induce the mutations of genes such as tumor suppressor p53 through its metabolite AFB1-8,9-exo-epoxide, which acts as a mutagen to react with DNA. In addition, recent study demonstrates AFB1 positively regulates type I insulin-like growth factor receptor (IGF-IR) signaling in hepatoma cells. The current study aims to determine the effects of AFB1 on Src kinase and insulin receptor substrate (IRS) in lung cancer cells and the effects of AFB1 on lung cancer cell migration. To this end, the effects of AFB1 on IRS expression, Src, Akt, and ERK phosphorylation were measured by Western blot analysis. The migration of lung cancer cells was detected by wound-healing assay. AFB1 downregulates IRS1 but paradoxically upregulates IRS2 through positive regulation of the stability of IRS2 and the proteasomal degradation of IRS1 in lung cancer cell lines A549 and SPCA-1. In addition, AFB1 induces Src, Akt, and ERK1/2 phosphorylation. Treatment of lung cancer cells with Src inhibitor saracatinib abrogates AFB1-induced IRS2 accumulation. Moreover, AFB1 stimulates lung cancer cell migration, which can be inhibited by saracatinib. We conclude that AFB1 may upregulate IRS2 and stimulate lung cancer cell migration through Src.
authors.affiliation: State Key Laboratory of Biotherapy, Section of Oncogene, West China Hospital, Sichuan University, No. 1 Ke Yuan 4 Lu, Chengdu, 610041, China.
authors.forename: Anguo
authors.initials: A
authors.lastname: Cui
authors.forename: Hui
authors.initials: H
authors.lastname: Hua
authors.forename: Ting
authors.initials: T
authors.lastname: Shao
authors.forename: Peiying
authors.initials: P
authors.lastname: Song
authors.forename: Qingbin
authors.initials: Q
authors.lastname: Kong
authors.forename: Ting
authors.initials: T
authors.lastname: Luo
authors.forename: Yangfu
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D016604:Aflatoxin B1 / Q000633:toxicity; D052117:Benzodioxoles / Q000008:administration & dosage; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000096:biosynthesis / Q000235:genetics*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D011799:Quinazolines / Q000008:administration & dosage; D015398:Signal Transduction / Q000187:drug effects; D019061:src-Family Kinases / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D052117:Benzodioxoles; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D011799:Quinazolines; C515233:saracatinib; D016604:Aflatoxin B1; D019061:src-Family Kinases
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