Adipocyte p62/SQSTM1 Suppresses Tumorigenesis through Opposite Regulations of Metabolism in Adipose Tissue and Tumor.

Abstract:

:Obesity is a leading risk factor for cancer. However, understanding the crosstalk between adipocytes and tumor cells in vivo, independently of dietary contributions, is a major gap in the field. Here we used a prostate cancer (PCa) mouse model in which the signaling adaptor p62/Sqstm1 is selectively inactivated in adipocytes. p62 loss in adipocytes results in increased osteopontin secretion, which mediates tumor fatty acid oxidation and invasion, leading to aggressive metastatic PCa in vivo. Furthermore, p62 deficiency triggers in adipocytes a general shutdown of energy-utilizing pathways through mTORC1 inhibition, which supports nutrient availability for cancer cells. This reveals a central role of adipocyte's p62 in the symbiotic adipose tissue-tumor collaboration that enables cancer metabolic fitness.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Huang J,Duran A,Reina-Campos M,Valencia T,Castilla EA,Müller TD,Tschöp MH,Moscat J,Diaz-Meco MT

doi

10.1016/j.ccell.2018.03.001

subject

Has Abstract

pub_date

2018-04-09 00:00:00

pages

770-784.e6

issue

4

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(18)30069-2

journal_volume

33

pub_type

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