TNFAIP8 regulates autophagy, cell steatosis, and promotes hepatocellular carcinoma cell proliferation.

Cell Death & Disease
Suryakant NitureDeepak Kumar

Abstract

Tumor necrosis factor-α-induced protein 8 (TNFAIP8) expression has been linked to tumor progression in various cancer types, but the detailed mechanisms of TNFAIP8 are not fully elucidated. Here we define the role of TNFAIP8 in early events associated with development of hepatocellular carcinoma (HCC). Increased TNFAIP8 levels in HCC cells enhanced cell survival by blocking apoptosis, rendering HCC cells more resistant to the anticancer drugs, sorafenib and regorafenib. TNFAIP8 also induced autophagy and steatosis in liver cancer cells. Consistent with these observations, TNFAIP8 blocked AKT/mTOR signaling and showed direct interaction with ATG3-ATG7 proteins. TNFAIP8 also exhibited binding with fatty acids and modulated expression of lipid/fatty-acid metabolizing enzymes. Chronic feeding of mice with alcohol increased hepatic levels of TNFAIP8, autophagy, and steatosis but not in high-fat-fed obese mice. Similarly, higher TNFAIP8 expression was associated with steatotic livers of human patients with a history of alcohol use but not in steatotic patients with no history of alcohol use. Our data indicate a novel role of TNFAIP8 in modulation of drug resistance, autophagy, and hepatic steatosis, all key early events in HCC progre...Continue Reading

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Citations

Jun 5, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Bingqing ShiPeng Gao
Nov 27, 2020·Journal of Hematology & Oncology·Haocai Chang, Zhengzhi Zou
Nov 24, 2020·The International Journal of Biochemistry & Cell Biology·Suryakant NitureDeepak Kumar
Sep 26, 2020·Life Sciences·Devivasha BordoloiAjaikuamr B Kunnumakkara
Feb 16, 2021·World Journal of Hepatology·Elias KouroumalisDimitrios N Samonakis
Mar 14, 2021·Cell Death & Disease·Yafei WuQin Li
May 6, 2021·International Journal of Molecular Sciences·So Young KimYung Hyun Choi
May 13, 2021·International Journal of Hepatology·Suryakant NitureDeepak Kumar
Jul 9, 2021·Frontiers in Cell and Developmental Biology·Dongmei FangMin Li
Jul 23, 2021·Journal of Chemotherapy·Mandeep Dahiya, Harish Dureja

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Methods Mentioned

BETA
xenograft
protein assay
PCR
ELISA
pull-down
lipidation

Software Mentioned

ImageJ
SPSS Statistics
Aperio
TMA Lab
Aperio eSlide Manager
Molecular Operating Environment ( MOE
MOE

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