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Tetraploidy is thought to be an intermediate on the path to aneuploidy, but the mechanistic relationship between the two states is poorly understood. Here, we show that spindle polarity (e.g. bipolarity or multipolarity) in tetraploid cells depends on the level of functional phosphorylated Eg5, a mitotic kinesin, localised to the spindle. Multipolar spindles are formed in cells with high levels of phosphorylated Eg5. This process is suppressed by inhibition of Eg5 or expression of a non-phosphorylatable Eg5 mutant, as well as by changing the balance between opposing forces required for centrosome separation. Tetraploid cells with high levels of functional Eg5 give rise to a heterogeneous aneuploid population through multipolar division, whereas cells with low levels of functional Eg5 continue to undergo bipolar division and remain tetraploid. Furthermore, Eg5 protein levels correlate with ploidy status in tumour specimens. We provide a novel explanation for the tetraploid intermediate model, i.e. spindle polarity and subsequent tetraploid cell behaviour are determined by the balance of forces generated by mitotic kinesins at the spindle.<\/jats:p>","DOI":"10.1242\/jcs.231530","type":"journal-article","created":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T14:25:11Z","timestamp":1574432711000},"source":"Crossref","is-referenced-by-count":13,"title":["The balance of forces generated by kinesins controls spindle polarity and chromosomal heterogeneity in tetraploid cells"],"prefix":"10.1242","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9875-6989","authenticated-orcid":false,"given":"Sei","family":"Shu","sequence":"first","affiliation":[{"name":"Graduate School of Medical Sciences, Kyushu University 1 Departments of Surgery and Science , , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 , Japan"},{"name":"Chugai Pharmaceutical Co. Ltd. 2 Product Research Department, Medical Affairs Division , , 200 Kajiwara, Kamakura, Kanagawa 247-8530 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1697-0178","authenticated-orcid":false,"given":"Makoto","family":"Iimori","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Kyushu University 3 Department of Molecular Cancer Biology , , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0311-9085","authenticated-orcid":false,"given":"Takeshi","family":"Wakasa","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Kyushu University 3 Department of Molecular Cancer Biology , , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 , Japan"},{"name":"Translational Research Laboratory, Taiho Pharmaceutical Co. Ltd. 4 , 224-2 Ebisuno Hiraishi, Kawauchi-Cho, Tokushima, 771-0194 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Ando","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Sciences, Kyushu University 1 Departments of Surgery and Science , , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5585-4244","authenticated-orcid":false,"given":"Hiroshi","family":"Saeki","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Sciences, Kyushu University 1 Departments of Surgery and Science , , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9636-1182","authenticated-orcid":false,"given":"Yoshinao","family":"Oda","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Sciences, Kyushu University 5 Department of Anatomic Pathology, Pathological Sciences , , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9763-9366","authenticated-orcid":false,"given":"Eiji","family":"Oki","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Sciences, Kyushu University 1 Departments of Surgery and Science , , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1532-3537","authenticated-orcid":false,"given":"Yoshihiko","family":"Maehara","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Sciences, Kyushu University 1 Departments of Surgery and Science , , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 , Japan"},{"name":"Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers 6 , 3-23-1 Shiobaru, Minami-ku, Fukuoka 815-8588 , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2019,12,13]]},"reference":[{"key":"2024061318415221800_JCS231530C1","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1007\/BF01665318","article-title":"Cytogenetic studies in patients with gastric cancer","volume":"15","author":"Abarbanel","year":"1991","journal-title":"World J. 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