Center for Animal Biotechnology and Genomics, Texas A&M University, College Station, TX 77843, USA.
Matrix Biol. 2010 Jun;29(5):369-82. doi: 10.1016/j.matbio.2010.04.001. Epub 2010 Apr 10.
Attachment and migration of trophectoderm (Tr) cells, hallmarks of blastocyst implantation in mammals, are unique uterine events. Secreted phosphoprotein 1 (SPP1) in the uterus binds integrins on conceptus Tr and uterine luminal epithelium (LE), affecting cell-cell and cell-matrix interactions. The signal transduction pathways activated by SPP1 and integrins in conceptuses have not been elucidated. Results of this study demonstrate that SPP1 binds alphavbeta3 and alpha5beta1 integrins to induce focal adhesion assembly, a prerequisite for adhesion and migration of Tr, through activation of: 1) P70S6K via crosstalk between FRAP1/mTOR and MAPK pathways; 2) mTOR, PI3K, MAPK3/MAPK1 (Erk1/2) and MAPK14 (p38) signaling to stimulate Tr cell migration; and 3) focal adhesion assembly and myosin II motor activity to induce migration of Tr cells. These cell signaling pathways, acting in concert, mediate adhesion, migration and cytoskeletal remodeling of Tr cells essential for expansion and elongation of conceptuses and attachment to uterine LE for implantation.
滋养层细胞的附着和迁移是哺乳动物胚胎着床的标志性事件，这是子宫内特有的事件。子宫中的分泌型磷蛋白 1（SPP1）与胚胎滋养层细胞和子宫腔上皮（LE）上的整合素结合，影响细胞-细胞和细胞-基质的相互作用。然而，SPP1 和整合素在胚胎中激活的信号转导途径尚未阐明。本研究结果表明，SPP1 通过与 FRAP1/mTOR 和 MAPK 途径的串扰激活 P70S6K，结合 alphavbeta3 和 alpha5beta1 整合素来诱导粘着斑的组装，这是滋养层细胞粘着和迁移的先决条件；通过：1）mTOR、PI3K、MAPK3/MAPK1（Erk1/2）和 MAPK14（p38）信号通路刺激滋养层细胞迁移；以及 3）粘着斑组装和肌球蛋白 II 运动活性诱导滋养层细胞迁移。这些协同作用的细胞信号通路介导了滋养层细胞的粘着、迁移和细胞骨架重塑，对于胚胎的扩张和伸长以及与子宫 LE 的附着和植入是必不可少的。
