Mierke Claudia Tanja
Faculty of Physics and Earth System Sciences, Peter Debye Institute of Soft Matter Physics, Biological Physics Division, Leipzig University, 04109 Leipzig, Germany.
Cells. 2025 Jun 20;14(13):943. doi: 10.3390/cells14130943.
Cancer metastasis constitutes a multifactorial phenomenon that continues to confound therapeutic strategies. The biochemical signals governing motile phenotypes have been extensively characterized, but mechanobiological interactions have only recently been integrated into cancer cell motility models and remain less well elucidated. The identification of the biochemically and mechanically controlled epithelial-mesenchymal transition (EMT) of cancer cells, which occurs either completely or partially, has led to a major breakthrough and a universal phenomenon in cancers. In addition, a relatively new theory based on mechanobiological aspects called "jamming-to-unjamming transition" is being proposed to explain the transition of cancer cells to an invasive phenotype. The latter transition may help to better understand the different types of 3D migration and invasion of cancer cells. Similarly to EMT, the transition from jamming to unjamming seems to be controlled by molecular and physical factors, including cell mechanics and mechanical cues from the extracellular matrix (ECM) of the tumor microenvironment (TME). It is challenging to grasp the distinctions between the transition from jamming to unjamming and EMT, as they appear to be the same at first glance. However, upon closer examination, the two transitions are quite separate. Moreover, it is still unclear whether both transitions may act synergistically. This review highlights the most important breakthroughs in the transition from jamming to unjamming, with a focus on mechanobiology and extracellular environmental aspects, and it compares them with those of EMT. In addition, the impact of the TME, such as ECM scaffold and cancer-associated fibroblasts (CAFs) on the jamming-to-unjamming transition is discussed. Finally, the research frontiers and future directions in the field of mechanobiological research in cancer metastasis are outlined.
癌症转移是一种多因素现象，仍然困扰着治疗策略。控制运动表型的生化信号已得到广泛表征，但机械生物学相互作用直到最近才被纳入癌细胞运动模型，且仍未得到充分阐明。癌细胞完全或部分发生的生化和机械控制的上皮-间质转化（EMT）的发现，带来了癌症研究中的一项重大突破和普遍现象。此外，一种基于机械生物学的相对较新的理论——“从堵塞到解堵塞转变”，正被提出来解释癌细胞向侵袭性表型的转变。后一种转变可能有助于更好地理解癌细胞的不同类型的三维迁移和侵袭。与EMT类似，从堵塞到解堵塞的转变似乎受分子和物理因素控制，包括细胞力学以及来自肿瘤微环境（TME）细胞外基质（ECM）的机械信号。要把握从堵塞到解堵塞的转变与EMT之间的区别具有挑战性，因为它们乍一看似乎相同。然而，仔细研究后会发现这两种转变截然不同。此外，尚不清楚这两种转变是否可能协同作用。本综述重点介绍了从堵塞到解堵塞转变方面的最重要突破，重点关注机械生物学和细胞外环境方面，并将它们与EMT的突破进行比较。此外，还讨论了TME（如ECM支架和癌症相关成纤维细胞（CAFs））对从堵塞到解堵塞转变的影响。最后，概述了癌症转移机械生物学研究领域的前沿研究和未来方向。
