Stat3 regulates centrosome clustering in cancer cells via Stathmin/PLK1

Edward J. Morris, Eiko Kawamura, Jordan A. Gillespie, Aruna Balgi, Nagarajan Kannan, William J. Muller, Michel Roberge, Shoukat Dedhar

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
Article number15289
JournalNature Communications
Volume8
DOIs
StatePublished - May 5 2017
Externally publishedYes

Fingerprint

Stathmin
Centrosome
inhibitors
Cluster Analysis
Tumors
cancer
Cells
tumors
Neoplasms
Depolymerization
Transcription
depolymerization
spindles
Phosphotransferases
cultured cells
viability
breast
depletion
Spindle Apparatus
Tumor Cell Line

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Morris, E. J., Kawamura, E., Gillespie, J. A., Balgi, A., Kannan, N., Muller, W. J., ... Dedhar, S. (2017). Stat3 regulates centrosome clustering in cancer cells via Stathmin/PLK1. Nature Communications, 8, [15289]. https://doi.org/10.1038/ncomms15289

Stat3 regulates centrosome clustering in cancer cells via Stathmin/PLK1. / Morris, Edward J.; Kawamura, Eiko; Gillespie, Jordan A.; Balgi, Aruna; Kannan, Nagarajan; Muller, William J.; Roberge, Michel; Dedhar, Shoukat.

In: Nature Communications, Vol. 8, 15289, 05.05.2017.

Research output: Contribution to journalArticle

Morris, EJ, Kawamura, E, Gillespie, JA, Balgi, A, Kannan, N, Muller, WJ, Roberge, M & Dedhar, S 2017, 'Stat3 regulates centrosome clustering in cancer cells via Stathmin/PLK1', Nature Communications, vol. 8, 15289. https://doi.org/10.1038/ncomms15289
Morris, Edward J. ; Kawamura, Eiko ; Gillespie, Jordan A. ; Balgi, Aruna ; Kannan, Nagarajan ; Muller, William J. ; Roberge, Michel ; Dedhar, Shoukat. / Stat3 regulates centrosome clustering in cancer cells via Stathmin/PLK1. In: Nature Communications. 2017 ; Vol. 8.
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