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The shear force generated by bloodstream provides mechanical signals regulating multiple responses of cells, including metastatic cancer cells, dispersing in blood vessels. We, therefore, studied the effect of shear flow on circulating CRC cells in the present study. The CRC cell line SW620 was subjected to shear flow of 12.5 dynes\/cm<jats:sup>2<\/jats:sup> for 1 and 2\u2009h separately. Resulting elevated caspase\u20109 and \u20103 indicated that shear flow initiated the apoptosis of SW620. Enlarged cell size associated with a higher level of cyclin D1 was coincident with the flow cytometric results indicating that the cell cycle was arrested at the G<jats:sub>1<\/jats:sub> phase. An elevated phosphor\u2010eNOS<jats:sup>S1177<\/jats:sup> increased the production of nitric oxide and led to reactive oxygen species\u2010mediated oxidative stress. Shear flow also regulated epithelial\u2013mesenchymal transition (EMT) by increasing E\u2010cadherin and ZO\u20101 while decreasing Snail and Twist1. The migration and invasion of sheared SW620 were also substantially decreased. Further investigations showed that mitochondrial membrane potential was significantly decreased, whereas mitochondrial mass and ATP production were not changed. In addition to the shear flow of 12.5 dynes\/cm<jats:sup>2<\/jats:sup>, the expressions of EMT were compared at lower (6.25 dynes\/cm<jats:sup>2<\/jats:sup>) and at higher (25 dynes\/cm<jats:sup>2<\/jats:sup>) shear flow. The results showed that lower shear flow increased mesenchymal characteristics and higher shear flow increased epithelial characteristics. Shear flow reduces the malignancy of CRC in their metastatic dispersal that opens up new ways to improve cancer therapies by applying a mechanical shear flow device.<\/jats:p>","DOI":"10.1002\/kjm2.12844","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T10:15:51Z","timestamp":1715940951000},"page":"650-659","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Mechanical shear flow regulates the malignancy of colorectal cancer cells"],"prefix":"10.1002","volume":"40","author":[{"given":"Yu\u2010Ting","family":"Tseng","sequence":"first","affiliation":[{"name":"Department of Biomedical Science and Environmental Biology, College of Life Science Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching\u2010Chung","family":"Tsai","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine I\u2010Shou University  Kaohsiung Taiwan"},{"name":"Department of Pediatrics, E\u2010Da Hospital I\u2010Shou University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping\u2010Chen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences National Sun Yat\u2010sen University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo\u2010Yan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Environmental Biology, College of Life Science Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2576-7289","authenticated-orcid":false,"given":"Sodio C. 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