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CTC reattachment has shown to be dependent on microtentacle (McTN) formation in vivo. However, the specific molecular mechanism of McTN formation in suspended cancer cells remains largely unclear. Here, we demonstrated that the activation of Notch\u20101 signaling triggers McTN formation to facilitate cell reattachment in suspended cell culture conditions. Moreover, molecular mechanistic studies revealed that McTN formation is governed by the balance between microtubule\u2010driven outgrowth and actomyosin\u2010driven cell contractility. The activation of Notch\u20101 downregulates the acetylation level of microtubules via the Cdc42\/HDAC6 pathway, which contributes to microtubule polymerization. Simultaneously, Notch\u20101 signaling\u2010induced Cdc42 activation also reduced phosphorylation of myosin regulatory light chain, leading to cell contractility attenuation. Altogether, these results defined a novel mechanism by which Notch\u20101 signaling disturbs the balance between the expansion of microtubules and contraction of the cortical actin, which promotes McTN formation and cell reattachment. Our findings provide a new perspective on the effective therapeutic target to prevent CTC reattachment.<\/jats:p>","DOI":"10.1111\/cas.15146","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T20:36:07Z","timestamp":1632861367000},"page":"4894-4908","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Notch\u20101 signaling promotes reattachment of suspended cancer cells by cdc42\u2010dependent microtentacles formation"],"prefix":"10.1111","volume":"112","author":[{"given":"Ping","family":"Li","sequence":"first","affiliation":[{"name":"Department of Biophysics School of Life Science and Technology University of Electronic Science and Technology of China Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biophysics School of Life Science and Technology University of Electronic 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