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To metastasize, breast cancer cells must detach from the main tumour mass and resist anoikis, a programmed cell death induced by lack of cell-extracellular matrix communication. Although cancer cells must detach to metastasize <jats:italic>in vivo<\/jats:italic>, the viability of floating cancer cells <jats:italic>in vitro<\/jats:italic> is rarely investigated. Here we show that co-treatment of anoikis-resistant MDA-MB-231 cells with metformin and 2-deoxy-D-glucose (2-DG) increased the percentage of floating cells, of which about 95% were viable. Floating cells resumed their proliferation once they were reseeded in the pharmacological compound-free medium. Similar effects on detachment were observed on anoikis-prone MCF-7 cells. Co-treatment of MDA-MB-231 cells with metformin and 2-DG induced a strong activation of AMP-activated protein kinase (AMPK), which was reduced by AMPK inhibitor compound C that prevented detachment of MDA-MB-231 cells. However, direct AMPK activators A-769662 and AICAR did not have any major effect on the percentage of floating MDA-MB-231 cells, indicating that AMPK activation is necessary but not sufficient for triggering detachment of cancer cells. Our results demonstrate that separate analysis of floating and attached cancer cells might be important for evaluation of anti-cancer agents.<\/jats:p>","DOI":"10.1038\/s41598-017-01801-5","type":"journal-article","created":{"date-parts":[[2017,5,5]],"date-time":"2017-05-05T11:30:00Z","timestamp":1493983800000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Combined treatment with Metformin and 2-deoxy glucose induces detachment of viable MDA-MB-231 breast cancer cells in vitro"],"prefix":"10.1038","volume":"7","author":[{"given":"Maru\u0161a","family":"Bizjak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Malava\u0161i\u010d","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klemen","family":"Dolinar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelka","family":"Pohar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergej","family":"Pirkmajer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mojca","family":"Pavlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,5,11]]},"reference":[{"key":"1801_CR1","doi-asserted-by":"publisher","first-page":"5652","DOI":"10.1200\/JCO.2006.06.5664","volume":"24","author":"BG Haffty","year":"2006","unstructured":"Haffty, B. G. et al. Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. J. Clin. Oncol. \n                           24, 5652\u20135657, doi:10.1200\/JCO.2006.06.5664 (2006).","journal-title":"J. Clin. Oncol."},{"key":"1801_CR2","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s10549-007-9756-8","volume":"111","author":"DSP Tan","year":"2008","unstructured":"Tan, D. S. P. et al. Triple negative breast cancer: molecular profiling and prognostic impact in adjuvant anthracycline-treated patients. Breast Cancer Res. Treat. \n                           111, 27\u201344, doi:10.1007\/s10549-007-9756-8 (2008).","journal-title":"Breast Cancer Res. Treat."},{"key":"1801_CR3","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/nrc1098","volume":"3","author":"IJ Fidler","year":"2003","unstructured":"Fidler, I. J. The pathogenesis of cancer metastasis: the\u2019seed and soil\u2019hypothesis revisited. Nat. Rev. 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