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

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

Nature communications (2017-05-06)
Edward J Morris, Eiko Kawamura, Jordan A Gillespie, Aruna Balgi, Nagarajan Kannan, William J Muller, Michel Roberge, Shoukat Dedhar
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-α-Tubulin antibody produced in mouse, clone DM1A, ascites fluid
Sigma-Aldrich
Anti-Aurora-A Kinase antibody, Mouse monoclonal, clone 35C1, purified from hybridoma cell culture