期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 216, 期 5, 页码 1108-1119出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20181288
关键词
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资金
- European Research Council [ERC 260464]
- European Foundation for the Study of Diabetes-Lilly
- Ministerio de Ciencia, Innovacion y Universidades [MICINN/SAF201679126-R]
- Comunidad de Madrid [B2017/BMD-3733, S2017/BMD-3727]
- BBVA Becas Leonardo a Investigadores y Creadores Culturales (Investigadores-BBVA-2017) [IN[17]_BBM_BAS_0066]
- Instituto de Salud Carlos III
- Federacion Espanola de Enfermedades Raras [PI16/01548]
- Junta de Castilla y Leon GRS [1587/A/17]
- Ministerio de Economia y Competitividad Retos [SAF2016-78711]
- Alan Morement Memorial Fund Cholangiocarcinoma Charity [2018/117]
- European Cooperation in Science and Technology Action [CA17112]
- European Foundation for Alcohol Research [EA14/18]
- Ministerio de Ciencia, Innovacion y Universidades
- Pro CNIC Foundation
Hepatocellular carcinoma (HCC) is the sixth most common cancer type and the fourth leading cause of cancer-related death. This cancer appears with higher incidence in men and during obesity; however, the specific mechanisms underlying this correlation are unknown. Adipose tissue, a key organ in metabolic syndrome, shows evident gender disparities in the production of adipokines. Levels of the important adipokine adiponectin decrease in men during puberty, as well as in the obese state. Here, we show that this decrease in adiponectin levels is responsible for the increased liver cancer risk in males. We found that testosterone activates the protein JNK in mouse and human adipocytes. JNK-mediated inhibition of adiponectin secretion increases liver cancer cell proliferation, since adiponectin protects against liver cancer development through the activation of AMP-activated protein kinase (AMPK) and p38a. This study provides insight into adipose tissue to liver crosstalk and its gender relation during cancer development, having the potential to guide strategies for new cancer therapeutics.
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