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 Advjournal_title
Science advancesauthors
Li Y,Mao AS,Seo BR,Zhao X,Gupta SK,Chen M,Han YL,Shih TY,Mooney DJ,Guo Mdoi
10.1126/sciadv.aax5611subject
Has Abstractpub_date
2020-01-22 00:00:00pages
eaax5611issue
4issn
2375-2548pii
aax5611journal_volume
6pub_type
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