TY - JOUR
T1 - Targeting PLK1 as a novel chemopreventive approach to eradicate preneoplastic mucosal changes in the head and neck
AU - de Boer, D.V.
AU - Martens-de Kemp, S.R.
AU - Buijze, M.
AU - Stigter-van Walsum, M.
AU - Bloemena, E.
AU - Dietrich, R.
AU - Leemans, C.R.
AU - van Beusechem, V.W.
AU - Braakhuis, B.J.M.
AU - Brakenhoff, R.H.
N1 - With supplementary materials
PY - 2017/11/17
Y1 - 2017/11/17
N2 - 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.
AB - 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.
KW - Head and neck squamous cell carcinoma
KW - Polo-like kinase 1
KW - Preneoplastic fields
KW - SiRNA screening
KW - Targeted treatment
UR - http://www.scopus.com/inward/record.url?scp=85034948598&partnerID=8YFLogxK
UR - https://pure.uva.nl/ws/files/29330122/17880_261239_5_SP.pdf
UR - https://pure.uva.nl/ws/files/29330124/17880_261240_2_SP.xls
U2 - https://doi.org/10.18632/oncotarget.17880
DO - https://doi.org/10.18632/oncotarget.17880
M3 - Article
C2 - 29228663
SN - 1949-2553
VL - 8
SP - 97928
EP - 97940
JO - Oncotarget
JF - Oncotarget
IS - 58
ER -