Mechanical Stretch Kills Transformed Cancer Cells

Ajay Tijore, Mingxi Yao, Yu Hsiu Wang, Yasaman Nematbakhsh, Anushya Hariharan, Chwee Teck Lim, Michael Sheetz

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Dec 10 2018
Externally publishedYes

Keywords

  • apoptosis
  • calpain
  • cancer treatment
  • cell stretching
  • DAPK1
  • malignant transformation
  • mechanical force
  • piezo calcium channel

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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