Oncotarget

Research Papers:

Loss of AIM2 expression promotes hepatocarcinoma progression through activation of mTOR-S6K1 pathway

Xiaomin Ma, Pengbo Guo, Yumin Qiu, Kun Mu, Lihui Zhu, Wei Zhao, Tao Li and Lihui Han _

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Oncotarget. 2016; 7:36185-36197. https://doi.org/10.18632/oncotarget.9154

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Abstract

Xiaomin Ma1, Pengbo Guo1, Yumin Qiu1, Kun Mu2, Lihui Zhu1, Wei Zhao1, Tao Li3, Lihui Han1

1Department of Immunology, Shandong University School of Medicine, Jinan 250012, China

2Department of Pathology, Shandong University School of Medicine, Jinan 250012, China

3Department of Gastroenterology, Provincial Hospital Affiliated with Shandong University, Jinan 250021, China

Correspondence to:

Lihui Han, email: [email protected]

Keywords: absent in melanoma 2, inflammasome, hepatocellular carcinoma, mammalian target of rapamycin, tumor progression

Received: January 06, 2016     Accepted: April 19, 2016     Published: May 04, 2016

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.


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