Identification of polo-like kinase 1 as a potential therapeutic target in anaplastic thyroid carcinoma

Tito Claudio Nappi, Paolo Salerno, Horst Zitzelsberger, Francesca Carlomagno, Giuliana Salvátore, Massimo Santoro

Research output: Contribution to journalArticle

Abstract

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and chemoresistant cancers. The serine/threonine kinase Polo-like kinase 1 (PLKl), a key regulator of multiple steps during mitotic progression, is highly expressed in ATC. Here, we used the BI 2536 PLKl inhibitor on ATC and nontransformed thyroid follicular cell lines. Our data show that ATC cells are addicted to high levels of FLKl activity for proliferation, survival, anchorage-independent growth, and tumorigenicity. On treatment with nanomolar doses of BI 2536, ATC cells progressed normally through S phase but died thereafter, directly from mitotic arrest. Immunofluorescence microscopy, immunoblot, and flow cytometry analysis showed that, on PLKl blockade, ATC cells arrested in prometaphase with a 4N DNA content. Treated ATC cells accumulated phosphohistone H3 and displayed characteristic mitotic (Polo) spindle aberrations. Nontransformed thyroid cells were 3.2-to 18.4-fold less susceptible to BI 2536-induced cell cycle effects compared with ATC cells. These findings identify PLKl as a promising target for the molecular therapy of ATC.

Original languageEnglish
Pages (from-to)1916-1923
Number of pages8
JournalCancer Research
Volume69
Issue number5
DOIs
Publication statusPublished - Mar 1 2009

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Identification of polo-like kinase 1 as a potential therapeutic target in anaplastic thyroid carcinoma'. Together they form a unique fingerprint.

  • Cite this