Compression-induced dedifferentiation of adipocytes promotes tumor progression.

Abstract:

:Dysregulated physical stresses are generated during tumorigenesis that affect the surrounding compliant tissues including adipocytes. However, the effect of physical stressors on the behavior of adipocytes and their cross-talk with tumor cells remain elusive. Here, we demonstrate that compression of cells, resulting from various types of physical stresses, can induce dedifferentiation of adipocytes via mechanically activating Wnt/β-catenin signaling. The compression-induced dedifferentiated adipocytes (CiDAs) have a distinct transcriptome profile, long-term self-renewal, and serial clonogenicity, but do not form teratomas. We then show that CiDAs notably enhance human mammary adenocarcinoma proliferation both in vitro and in a xenograft model, owing to myofibrogenesis of CiDAs in the tumor-conditioned environment. Collectively, our results highlight unique physical interplay in the tumor ecosystem; tumor-induced physical stresses stimulate de novo generation of CiDAs, which feedback to tumor growth.

journal_name

Sci Adv

journal_title

Science advances

authors

Li Y,Mao AS,Seo BR,Zhao X,Gupta SK,Chen M,Han YL,Shih TY,Mooney DJ,Guo M

doi

10.1126/sciadv.aax5611

subject

Has Abstract

pub_date

2020-01-22 00:00:00

pages

eaax5611

issue

4

issn

2375-2548

pii

aax5611

journal_volume

6

pub_type

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