title: Loss of AIM2 expression promotes hepatocarcinoma progression through activation of mTOR-S6K1 pathway.
abstract: Absent in melanoma (AIM2) is a member of the interferon-inducible HIN-200 protein family and is recently recognized to play an important dual role in both innate immunity and tumor pathology. However, the role of AIM2 in the development of hepatocellular carcinoma (HCC) remains to be clarified. Here we showed that AIM2 expression was significantly decreased in liver cancer tissues, and loss of its expression was significantly correlated with more advanced tumor progression. Exogenous overexpression of AIM2 in HCC cells suppressed mammalian target of rapamycin (mTOR)-S6K1 pathway and further inhibited proliferation, colony formation and invasion of HCC cells. On the contrary, block of AIM2 in HCC cells induced (mTOR)-S6K1 pathway activation and thus promoted HCC progression. Treatment with mTOR pathway inhibitor rapamycin further verified its contribution to HCC progression in AIM2 absent HCC cells. Thus, these data suggested that AIM2 played a critical role as a tumor suppressor and might serve as a potential therapeutic target for future development of AIM2-based gene therapy for human liver cancer. This study also paves a new avenue to treat AIM2-deficient cancer by suppression of mTOR.
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Pengbo
authors.initials: P
authors.lastname: Guo
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Pathology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Mu
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, Provincial Hospital Affiliated with Shandong University, Jinan 250021, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Immunology, Shandong University School of Medicine, Jinan 250012, China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Han
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D034622:RNA Interference; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: C410167:AIM2 protein, human; D004268:DNA-Binding Proteins; C546842:MTOR protein, human; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1
keywords: absent in melanoma 2; hepatocellular carcinoma; inflammasome; mammalian target of rapamycin; tumor progression