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Piezo1 activation a...
Piezo1 activation attenuates thrombin-induced blebbing in breast cancer cells
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- O'Callaghan, Paul (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Engberg, Adam (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Eriksson, Olle (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Fatsis-Kavalopoulos, Nikos (author)
- Uppsala Univ, Dept Med Biochem & Microbiol, S-75123 Uppsala, Sweden.
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- Stelzl, Christina (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Sanchez, Gonzalo (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Idevall Hagren, Olof, 1980- (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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- Kreuger, Johan, 1972- (author)
- Uppsala universitet,Institutionen för medicinsk cellbiologi
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(creator_code:org_t)
- 2022-04-01
- 2022
- English.
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In: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 135:7
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https://uu.diva-port... (primary) (Raw object)
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Abstract
Subject headings
Close
- Cancer cells exploit a variety of migration modes to leave primary tumors and establish metastases, including amoeboid cell migration, which is typically reliant on bleb formation. Here we demonstrate that thrombin induces dynamic blabbing in the MDA-MB-231 breast cancer cell line and confirm that protease-activated receptor 1 (PAR1) activation is sufficient to induce this effect. Cell confinement has been implicated as a driving force in bleb-based migration. Unexpectedly, we found that gentle contact compression, exerted using a custom built 'cell press' to mechanically stimulate cells, reduced thrombin-induced blebbing. Thrombin-induced blebbing was similarly attenuated using the small molecule Yoda1, an agonist of the mechanosensitive Ca2+ channel Piezo1, and this attenuation was impaired in Piezo1-depleted cells. Additionally, Piezo1 activation suppressed thrombin-induced phosphorylation of ezrin, radixin and moesin (ERM) proteins, which are implicated in the blabbing process. Our results provide mechanistic insights into Piezo1 activation as a suppressor of dynamic blebbing, specifically that which is induced by thrombin.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Piezo1
- Thrombin
- Blebbing
- Breast cancer
Publication and Content Type
- ref (subject category)
- art (subject category)
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