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Targeting PLK1 as a novel chemopreventive approach to eradicate preneoplastic mucosal changes in the head and neck.


ABSTRACT: Head and neck squamous cell carcinomas (HNSCC) and local relapses thereof develop in preneoplastic fields in the mucosal linings of the upper aerodigestive tract. These fields are characterized by tumor-associated genetic changes, are frequently dysplastic and occasionally macroscopically visible. Currently, no adequate treatment options exist to prevent tumor development. Array-based screening with a panel of tumor-lethal small interfering RNAs (siRNAs) identified Polo-like kinase 1 (PLK1) as essential for survival of preneoplastic cells. Inhibition of PLK1 caused cell death of preneoplastic and HNSCC cells, while primary cells were hardly affected. Both siRNAs and small molecule inhibitors caused a strong G2/M cell cycle arrest accompanied by formation of monopolar spindles. In a xenografted mouse model PLK1 caused a significant tumor growth delay and cures, while chemoradiation had no effect. Thus, PLK1 seems to be a promising target for chemopreventive treatment of preneoplastic cells, and could be applied to prevent HNSCC and local relapses.

SUBMITTER: de Boer DV 

PROVIDER: S-EPMC5716703 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Targeting PLK1 as a novel chemopreventive approach to eradicate preneoplastic mucosal changes in the head and neck.

de Boer D Vicky DV   Martens-de Kemp Sanne R SR   Buijze Marijke M   Stigter-van Walsum Marijke M   Bloemena Elisabeth E   Dietrich Ralf R   Leemans C René CR   van Beusechem Victor W VW   Braakhuis Boudewijn J M BJM   Brakenhoff Ruud H RH  

Oncotarget 20170516 58


Head and neck squamous cell carcinomas (HNSCC) and local relapses thereof develop in preneoplastic fields in the mucosal linings of the upper aerodigestive tract. These fields are characterized by tumor-associated genetic changes, are frequently dysplastic and occasionally macroscopically visible. Currently, no adequate treatment options exist to prevent tumor development. Array-based screening with a panel of tumor-lethal small interfering RNAs (siRNAs) identified <i>Polo-like kinase 1</i> (<i>  ...[more]

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