Targeting PLK1 as a novel chemopreventive approach to eradicate preneoplastic mucosal changes in the head and neck
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. C...
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| Vydáno v: | Oncotarget Ročník 8; číslo 58; s. 97928 |
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| Hlavní autoři: | , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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17.11.2017
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| ISSN: | 1949-2553, 1949-2553 |
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| 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
(
) 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. |
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| AbstractList | 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.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. 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 ( ) 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. |
| Author | Buijze, Marijke Stigter-van Walsum, Marijke Dietrich, Ralf Leemans, C René Braakhuis, Boudewijn J M van Beusechem, Victor W Martens-de Kemp, Sanne R Bloemena, Elisabeth Brakenhoff, Ruud H de Boer, D Vicky |
| Author_xml | – sequence: 1 givenname: D Vicky surname: de Boer fullname: de Boer, D Vicky organization: Department of Otolaryngology-Head and Neck Surgery, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands – sequence: 2 givenname: Sanne R surname: Martens-de Kemp fullname: Martens-de Kemp, Sanne R organization: Department of Otolaryngology-Head and Neck Surgery, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands – sequence: 3 givenname: Marijke surname: Buijze fullname: Buijze, Marijke organization: Department of Otolaryngology-Head and Neck Surgery, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands – sequence: 4 givenname: Marijke surname: Stigter-van Walsum fullname: Stigter-van Walsum, Marijke organization: Department of Otolaryngology-Head and Neck Surgery, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands – sequence: 5 givenname: Elisabeth surname: Bloemena fullname: Bloemena, Elisabeth organization: Department of Maxillofacial Surgery/Oral Pathology, Academic Center for Dentistry Amsterdam (ACTA), Amsterdam, The Netherlands – sequence: 6 givenname: Ralf surname: Dietrich fullname: Dietrich, Ralf organization: German Fanconi-Anemia-Help e.V., Unna-Siddinghausen, Germany – sequence: 7 givenname: C René surname: Leemans fullname: Leemans, C René organization: Department of Otolaryngology-Head and Neck Surgery, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands – sequence: 8 givenname: Victor W surname: van Beusechem fullname: van Beusechem, Victor W organization: Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands – sequence: 9 givenname: Boudewijn J M surname: Braakhuis fullname: Braakhuis, Boudewijn J M organization: Department of Otolaryngology-Head and Neck Surgery, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands – sequence: 10 givenname: Ruud H surname: Brakenhoff fullname: Brakenhoff, Ruud H organization: Department of Otolaryngology-Head and Neck Surgery, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands |
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| Keywords | polo-like kinase 1 siRNA screening preneoplastic fields head and neck squamous cell carcinoma targeted treatment |
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| Title | Targeting PLK1 as a novel chemopreventive approach to eradicate preneoplastic mucosal changes in the head and neck |
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