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Publication : Stat3 regulates centrosome clustering in cancer cells via Stathmin/PLK1.

First Author  Morris EJ Year  2017
Journal  Nat Commun Volume  8
Pages  15289 PubMed ID  28474672
Mgi Jnum  J:249568 Mgi Id  MGI:5921498
Doi  10.1038/ncomms15289 Citation  Morris EJ, et al. (2017) Stat3 regulates centrosome clustering in cancer cells via Stathmin/PLK1. Nat Commun 8:15289
abstractText  Cancer cells frequently have amplified centrosomes that must be clustered together to form a bipolar mitotic spindle, and targeting centrosome clustering is considered a promising therapeutic strategy. A high-content chemical screen for inhibitors of centrosome clustering identified Stattic, a Stat3 inhibitor. Stat3 depletion and inhibition in cancer cell lines and in tumours in vivo caused significant inhibition of centrosome clustering and viability. Here we describe a transcription-independent mechanism for Stat3-mediated centrosome clustering that involves Stathmin, a Stat3 interactor involved in microtubule depolymerization, and the mitotic kinase PLK1. Furthermore, PLK4-driven centrosome amplified breast tumour cells are highly sensitive to Stat3 inhibitors. We have identified an unexpected role of Stat3 in the regulation of centrosome clustering, and this role of Stat3 may be critical in identifying tumours that are sensitive to Stat3 inhibitors.
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