Compression-induced dedifferentiation of adipocytes promotes tumor progression

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). Dysregulated physical stresses are generated...

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Bibliographic Details
Main Authors: Li, Yiwei, Mao, Angelo S, Seo, Bo Ri, Zhao, Xing, Gupta, Satish Kumar, Chen, Maorong, Han, Yu Long, Shih, Ting-Yu, Mooney, David J, Guo, Ming
Other Authors: Massachusetts Institute of Technology. Department of Mechanical Engineering
Format: Article
Language:English
Published: American Association for the Advancement of Science (AAAS) 2021
Online Access:https://hdl.handle.net/1721.1/136304
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Summary:Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). 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.