Aslemarz Azam, Fagotto-Kaufmann Marie, Ruppel Artur, Fagotto-Kaufmann Christine, Balland Martial, Lasko Paul, Fagotto François
CRBM, University of Montpellier and CNRS, Montpellier, 34293, France.
Dept. of Biology, McGill University, Montreal, QC, H3A1B1, Canada.
EMBO J. 2025 Jan;44(1):75-106. doi: 10.1038/s44318-024-00309-9. Epub 2024 Nov 21.
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.
上皮细胞黏附分子（EpCAM）及其近亲滋养层细胞表面抗原2（Trop2）是众所周知的癌组织细胞表面标志物，但其在癌症转移中的潜在作用仍不清楚。然而，已知它们会下调肌球蛋白依赖性收缩力，这是参与黏附和迁移的一个关键参数。我们在此使用MCF7细胞球体作为体外模型，研究上皮性乳腺癌细胞中通常发现的高EpCAM和Trop2水平对形态发生的影响。有趣的是，EpCAM缺失会刺激球体的黏附性铺展，而Trop2缺失则产生相反的效果。结合细胞生物学和生物物理学方法，我们证明，虽然EpCAM和Trop2都有助于适度的细胞收缩力，但它们的缺失通过影响细胞和组织界面处皮质张力的平衡，对“湿润”底物（此处为基质和相邻细胞）的过程产生不同影响。这些不同的表型可以通过在特定界面的部分富集来解释。我们的数据与EpCAM-Trop2这一对分子作为调节黏附与迁移行为的机械调节器的作用一致。
