Increasing β-catenin/Wnt3A activity levels drive mechanical strain-induced cell cycle progression through mitosis

摘要

Tissues and organs can both produce and respond to physical forces. For example, the lungs expand and contract; the heart pumps blood; and bones and muscles grow or shrink depending on how much they are used. These responses are possible because cells contain proteins that can respond to physical forces. One of the best studied of these is a protein called β-catenin, which increases the activity of genes that trigger cells to divide to promote the expansion of tissues. β-catenin is over-active in many types of cancer cells where it contributes to tumor growth. In addition to being switched on by mechanical force, β-catenin is also activated when cells detect a signal molecule called Wnt. Cells cycle through a series of stages known as the cell cycle to ensure that they only divide when they are fully prepared to do so. Benham-Pyle et al. investigated if physical force and Wnt activate β-catenin in the same way or if they have different effects on cell division. The experiments were conducted on dog kidney cells that had left the cell cycle and had therefore temporarily stopped dividing. Physical forces, such as stretching, resulted in β-catenin being modified by an enzyme called SRC kinase, which allowed the cells to re-enter the cell cycle. On the other hand, Wnt stabilized β-catenin and temporarily increased the number of cell divisions. When mechanical stretch and Wnt signaling were combined, the cells were more likely to re-enter the cell cycle and divide compared to either stimulus alone. These data suggest that physical force and Wnt signaling affect β-catenin differently and that they can therefore have a greater effect on cell or tissue growth when they act together than on their own. The findings of Benham-Pyle et al. show that β-catenin is not simply switched on or off, but can have different levels of activity depending on the input the cells are receiving. Future experiments will test whether these mechanisms also exist in three-dimensional tissues, which will help us understand how organs develop.