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Compression-induced dedifferentiation of adipocytes promotes tumor progression.
Science Advances ( IF 11.7 ) Pub Date : 2020-01-22 , DOI: 10.1126/sciadv.aax5611
Yiwei Li 1 , Angelo S Mao 2, 3 , Bo Ri Seo 2, 3 , Xing Zhao 1 , Satish Kumar Gupta 1 , Maorong Chen 4 , Yu Long Han 1 , Ting-Yu Shih 2, 3 , David J Mooney 2, 3 , Ming Guo 1
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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.

中文翻译:

压缩诱导的脂肪细胞去分化促进肿瘤进展。

在肿瘤发生过程中产生失调的身体压力,影响周围的顺应性组织,包括脂肪细胞。然而,物理应激源对脂肪细胞行为及其与肿瘤细胞的串扰的影响仍然难以捉摸。在这里,我们证明了由各种类型的物理压力导致的细胞压缩可通过机械激活Wnt /β-catenin信号传导诱导脂肪细胞去分化。压缩诱导的去分化脂肪细胞(CiDAs)具有独特的转录组特征,长期自我更新和连续克隆形成性,但不形成畸胎瘤。然后,我们显示,由于CiDAs在肿瘤条件下的环境中的肌纤维发生,CiDAs在体外和异种移植模型中均能显着增强人乳腺腺癌的增殖。总的来说,我们的结果强调了肿瘤生态系统中独特的物理相互作用;肿瘤引起的物理压力刺激了从头产生CiDAs,CiDAs反馈到肿瘤生长。
更新日期:2020-01-23
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