Department of Physiology, Biophysics and Neuroscience, CINVESTAV-IPN, Av. Politécnico Nacional 2508, 07360 Mexico City, Mexico.
Arch Biochem Biophys. 2012 Dec 15;528(2):148-55. doi: 10.1016/j.abb.2012.08.011. Epub 2012 Sep 13.
The adaptation of GH(3) cells to different microenvironments is a consequence of a partial compromise with the tumor phenotype. A collagen type IV enriched microenvironment favors an invasive phenotype and increases the substrate adhesion capacity, whereas it decreases the phosphorylation of the regulatory myosin light chain and the aggregation capacity. In contrast, the higher internal tension and increased aggregation capacity induced by collagen type I/III are factors that reduce the invasion rate. Our results show, for the first time, the importance of collagen subtypes in determining the migratory strategy: collagen I/III favors mesenchymal-like motility, whereas collagen type IV induces an ameboid-type displacement. The reciprocal modulation of the myosin light chain kinase and the Rho-kinase determines the invasive capacity through changes in tissue cohesion, extracellular matrix affinity, regulatory myosin light chain phosphorylation and spatial distribution. The collagen subtype determines which of the mechano-transduction signaling pathways will regulate the tensional homeostasis and affect the invasion ability as well as the preferred migration strategy of the cells.
GH(3)细胞对不同微环境的适应是与肿瘤表型部分妥协的结果。富含 IV 型胶原的微环境有利于侵袭表型，并增加基质黏附能力，而降低调节性肌球蛋白轻链的磷酸化和聚集能力。相比之下，I/III 型胶原诱导的更高的内部张力和增加的聚集能力是降低入侵率的因素。我们的结果首次表明胶原亚型在决定迁移策略方面的重要性：I/III 型胶原有利于间充质样运动，而 IV 型胶原诱导阿米巴样位移。肌球蛋白轻链激酶和 Rho 激酶的相互调节通过改变组织内聚力、细胞外基质亲和力、调节性肌球蛋白轻链磷酸化和空间分布来决定侵袭能力。胶原亚型决定了哪种机械转导信号通路将调节张力平衡，并影响细胞的侵袭能力以及首选的迁移策略。
