ROCK-generated contractility regulates breast epithelial cell differentiation in response to the physical properties of a three-dimensional collagen matrix.
ROCK-generated contractility regulates breast epithelial cell differentiation in response to the physical properties of a three-dimensional collagen matrix.
复制标题
岩石生成的收缩力调节乳房上皮细胞分化，以响应三维胶原基质的物理特性。
DOI：
10.1083/jcb.200305010
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发表时间：
2003-11-10
影响因子：
7.8
通讯作者：
Keely, Patricia J
中科院分区：
文献类型：
--
作者：
Wozniak, Michele A;Desai, Radhika;Solski, Patricia A;Der, Channing J;Keely, Patricia J
乳腺上皮细胞在漂浮的三维(3D)胶原凝胶中培养时会分化为小管，但当细胞在附着在培养皿上的相同胶原基质中培养时就不会分化为小管。这些观察表明，胶原基质的生物物理性质调节上皮分化，但发生这种情况的机制尚不清楚。小管的形成需要漂浮的胶原凝胶通过Rho和岩石介导的收缩来收缩。岩石介导的收缩能力降低了漂浮的3D胶原凝胶中的Rho活性，并对应于定位于3D基质粘连的Y397处磷酸化的FAK的丢失。增加漂浮的3D胶原凝胶的密度也扰乱了小管的形成，促进了FAK的磷酸化，并维持了较高的Rho活性。这些数据证明了这一新的发现，即乳腺上皮细胞通过岩石介导的收缩和随后Rho和FAK功能的下调来感知环境的刚性或密度，这是乳房上皮小管形成所必需的。
Breast epithelial cells differentiate into tubules when cultured in floating three-dimensional (3D) collagen gels, but not when the cells are cultured in the same collagen matrix that is attached to the culture dish. These observations suggest that the biophysical properties of collagenous matrices regulate epithelial differentiation, but the mechanism by which this occurs is unknown. Tubulogenesis required the contraction of floating collagen gels through Rho and ROCK-mediated contractility. ROCK-mediated contractility diminished Rho activity in a floating 3D collagen gel, and corresponded to a loss of FAK phosphorylated at Y397 localized to 3D matrix adhesions. Increasing the density of floating 3D collagen gels also disrupted tubulogenesis, promoted FAK phosphorylation, and sustained high Rho activity. These data demonstrate the novel finding that breast epithelial cells sense the rigidity or density of their environment via ROCK-mediated contractility and a subsequent down-regulation of Rho and FAK function, which is necessary for breast epithelial tubulogenesis to occur.