PT  - JOURNAL ARTICLE
AU  - Tijore, Ajay
AU  - Yao, Mingxi
AU  - Wang, Yu-Hsiu
AU  - Nematbakhsh, Yasaman
AU  - Hariharan, Anushya
AU  - Teck Lim, Chwee
AU  - Sheetz, Michael
TI  - Mechanical Stretch Kills Transformed Cancer Cells
AID  - 10.1101/491746
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 491746
4099  - http://biorxiv.org/content/early/2018/12/10/491746.short
4100  - http://biorxiv.org/content/early/2018/12/10/491746.full
AB  - Transformed cancer cells differ from normal cells in several important features like anchorage independence, Warburg effect and mechanosensing. Consequently, transformed cancer cells develop an anaplastic morphology and respond aberrantly to external mechanical forces. Consistent with altered mechano-responsiveness, here we show that transformed cancer cells from many different tissues have reduced growth and become apoptotic upon cyclic stretch as do normal cells after the transformation. When matrix rigidity sensing is restored in transformed cancer cells, they survive and grow faster on soft surface upon cyclic stretch like normal cells but undergo anoikis without stretch by activation of death associated protein kinase1 (DAPK1). In contrast, stretch-dependent apoptosis (mechanoptosis) of transformed cells is driven by stretch-mediated calcium influx and calcium-dependent calpain 2 protease activation on both collagen and fibronectin matrices. Further, mechanosensitive calcium channel, Piezo1 is needed for mechanoptosis. Thus, cyclic stretching of transformed cells from different tissues activates apoptosis, whereas similar stretching of normal cells stimulates growth.