An EpCAM/Trop2 mechanostat differentially regulates collective behaviour of human carcinoma cells.

IF 9.4 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
EMBO Journal Pub Date : 2025-01-01 Epub Date: 2024-11-21 DOI:10.1038/s44318-024-00309-9
Azam Aslemarz, Marie Fagotto-Kaufmann, Artur Ruppel, Christine Fagotto-Kaufmann, Martial Balland, Paul Lasko, François Fagotto
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引用次数: 0

Abstract

EpCAM and its close relative Trop2 are well-known cell surface markers of carcinoma, but their potential role in cancer metastasis remains unclear. They are known, however, to downregulate myosin-dependent contractility, a key parameter involved in adhesion and migration. We investigate here the morphogenetic impact of the high EpCAM and Trop2 levels typically found in epithelial breast cancer cells, using spheroids of MCF7 cells as an in vitro model. Intriguingly, EpCAM depletion stimulated spheroid cohesive spreading, while Trop2 depletion had the opposite effect. Combining cell biological and biophysical approaches, we demonstrate that while EpCAM and Trop2 both contribute to moderate cell contractility, their depletions differentially impact on the process of "wetting" a substrate, here both matrix and neighboring cells, by affecting the balance of cortical tension at cell and tissue interfaces. These distinct phenotypes can be explained by partial enrichment at specific interfaces. Our data are consistent with the EpCAM-Trop2 pair acting as a mechanostat that tunes adhesive and migratory behaviours.

EpCAM/Trop2机械调节器可对人类癌细胞的集体行为进行不同程度的调节。
EpCAM 及其近亲 Trop2 是众所周知的癌细胞表面标志物,但它们在癌症转移中的潜在作用仍不清楚。但已知它们会下调肌球蛋白依赖性收缩力,而肌球蛋白依赖性收缩力是参与粘附和迁移的关键参数。在此,我们以 MCF7 细胞球体为体外模型,研究了上皮乳腺癌细胞中通常存在的高水平 EpCAM 和 Trop2 对形态发生的影响。耐人寻味的是,EpCAM耗竭会刺激球体内聚扩散,而Trop2耗竭则产生相反的效果。结合细胞生物学和生物物理学方法,我们证明,虽然 EpCAM 和 Trop2 都有助于缓和细胞收缩性,但它们的耗竭会通过影响细胞和组织界面的皮质张力平衡,对基质(这里包括基质和邻近细胞)的 "润湿 "过程产生不同的影响。这些不同的表型可以通过特定界面的部分富集来解释。我们的数据表明,EpCAM-Trop2 对是一种调节粘附和迁移行为的机械调节器。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
EMBO Journal
EMBO Journal 生物-生化与分子生物学
CiteScore
18.90
自引率
0.90%
发文量
246
审稿时长
1.5 months
期刊介绍: The EMBO Journal has stood as EMBO's flagship publication since its inception in 1982. Renowned for its international reputation in quality and originality, the journal spans all facets of molecular biology. It serves as a platform for papers elucidating original research of broad general interest in molecular and cell biology, with a distinct focus on molecular mechanisms and physiological relevance. With a commitment to promoting articles reporting novel findings of broad biological significance, The EMBO Journal stands as a key contributor to advancing the field of molecular biology.
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