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Biol."],"abstract":"<jats:p>In this study, we evaluated changes in focal adhesions (FAs) in two types of breast cancer cell (BCC) lines (differentiated MCF-7 and the triple-negative MDA-MB-231 cell line) exposed to simulated microgravity (s-\u03bc<jats:italic>g<\/jats:italic>) created by a random positioning machine (RPM) for 24 h. After exposure, the BCC changed their growth behavior and exhibited two phenotypes in RPM samples: one portion of the cells grew as a normal two-dimensional monolayer [adherent (AD) BCC], while the other portion formed three-dimensional (3D) multicellular spheroids (MCS). After 1 h and 30 min (MDA-MB-231) and 1 h 40 min (MCF-7), the MCS adhered completely to the slide flask bottom. After 2 h, MDA-MB-231 MCS cells started to migrate, and after 6 h, a large number of the cells had left the MCS and continued to grow in a scattered pattern, whereas MCF-7 cells were growing as a confluent monolayer after 6 h and 24 h. We investigated the genes associated with the cytoskeleton, the extracellular matrix and FAs. <jats:italic>ACTB, TUBB, FN1, FAK1<\/jats:italic>, and <jats:italic>PXN<\/jats:italic> gene expression patterns were not significantly changed in MDA-MB-231 cells, but we observed a down-regulation of <jats:italic>LAMA3, ITGB1<\/jats:italic> mRNAs in AD cells and of <jats:italic>ITGB1, TLN1<\/jats:italic> and <jats:italic>VCL<\/jats:italic> mRNAs in MDA-MB-231 MCS. RPM-exposed MCF-7 cells revealed a down-regulation in the gene expression of <jats:italic>FAK1, PXN, TLN1, VCL<\/jats:italic> and <jats:italic>CDH1<\/jats:italic> in AD cells and <jats:italic>PXN, TLN<\/jats:italic> and <jats:italic>CDH1<\/jats:italic> in MCS. An interaction analysis of the examined genes involved in 3D growth and adhesion indicated a central role of fibronectin, vinculin, and E-cadherin. Live cell imaging of eGFP-vinculin in MCF-7 cells confirmed these findings. \u03b2-catenin-transfected MCF-7 cells revealed a nuclear expression in 1<jats:italic>g<\/jats:italic> and RPM-AD cells. The target genes <jats:italic>BCL9, MYC<\/jats:italic> and <jats:italic>JUN<\/jats:italic> of the Wnt\/\u03b2-catenin signaling pathway were differentially expressed in RPM-exposed MCF-7 cells. These findings suggest that vinculin and \u03b2-catenin are key mediators of BCC to form MCS during 24 h of RPM-exposure.<\/jats:p>","DOI":"10.3389\/fcell.2021.672098","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T06:51:42Z","timestamp":1625035902000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":28,"title":["Alterations of Growth and Focal Adhesion Molecules in Human Breast Cancer Cells Exposed to the Random Positioning Machine"],"prefix":"10.3389","volume":"9","author":[{"given":"Jayashree","family":"Sahana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Corydon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Wehland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Kr\u00fcger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"Kopp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Melnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kahlert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Borna","family":"Relja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Infanger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Grimm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1111\/bcpt.12561","article-title":"Scaffold-free tissue formation under real and simulated microgravity conditions.","volume":"119","author":"Aleshcheva","year":"2016","journal-title":"Basic Clin. 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