Skip to main content
Erschienen in: Journal of Cancer Research and Clinical Oncology 10/2019

04.09.2019 | Original Article – Cancer Research

Stress-triggered YAP1/SOX2 activation transcriptionally reprograms head and neck squamous cell carcinoma for the acquisition of stemness

verfasst von: Hirofumi Omori, Kuniaki Sato, Takafumi Nakano, Takahiro Wakasaki, Satoshi Toh, Kenichi Taguchi, Takashi Nakagawa, Muneyuki Masuda

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 10/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The clinical importance of cancer stem cells (CSCs) in head and neck squamous cell carcinoma (HNSCC) is well recognized. However, a reliable method for the detection of functioning CSC has not yet been established. We hypothesized that YAP1, a transcriptional coactivator, and SOX2, a master transcription factor of SCC, may cooperatively induce stemness through transcriptional reprogramming.

Methods

We immunohistochemically examined the expression of SOX2 and YAP1 in the CD44 variant 9 (CD44v9)-positive invasion front. A CSC-inducible module was identified through a combination of siRNAs and sphere formation assays. YAP1 and SOX2 interactions were analyzed in vitro.

Results

The triple overexpression of SOX2, YAP1, and CD44v9 was significantly associated with poor prognosis. TCGA data revealed that the CSC-inducible module, which was related to EMT and angiogenesis, was significantly correlated with poor prognosis. The KLF7 expression, representatively chosen from the module, also correlated with poor prognosis and was essential for sphere formation and CSC propagation. Sphere stress-activated YAP1 enhanced SOX2 activity.

Conclusions

The stress-triggered activation of YAP1/SOX2 transcriptionally reprograms HNSCC for the acquisition of stemness. Triple SOX2, YAP1, and CD44v9 immunostaining assays may be useful for the selection of high-risk patients with functioning CSCs, and YAP1 targeting may lead to the development of a CSC-targeting therapy.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
Zurück zum Zitat Dong Z, Liu G, Huang B, Sun J, Wu D (2014) Prognostic significance of SOX2 in head and neck cancer: a meta-analysis. Int J Clin Exp Med 7:5010–5020PubMedPubMedCentral Dong Z, Liu G, Huang B, Sun J, Wu D (2014) Prognostic significance of SOX2 in head and neck cancer: a meta-analysis. Int J Clin Exp Med 7:5010–5020PubMedPubMedCentral
Zurück zum Zitat Masuda M, Wakasaki T, Toh S (2016) Stress-triggered atavistic reprogramming (STAR) addiction: driving force behind head and neck cancer? Am J Cancer Res 6:1149–1166PubMedPubMedCentral Masuda M, Wakasaki T, Toh S (2016) Stress-triggered atavistic reprogramming (STAR) addiction: driving force behind head and neck cancer? Am J Cancer Res 6:1149–1166PubMedPubMedCentral
Zurück zum Zitat Watanabe H et al (2014) SOX2 and p63 colocalize at genetic loci in squamous cell carcinomas. J Clin Investig 124:1636–1645CrossRefPubMed Watanabe H et al (2014) SOX2 and p63 colocalize at genetic loci in squamous cell carcinomas. J Clin Investig 124:1636–1645CrossRefPubMed
Zurück zum Zitat Zhu Q, Liang X, Dai J, Guan X (2015) Prostaglandin transporter, SLCO2A1, mediates the invasion and apoptosis of lung cancer cells via PI3K/AKT/mTOR pathway. Int J Clin Exp Pathol 8:9175–9181PubMedPubMedCentral Zhu Q, Liang X, Dai J, Guan X (2015) Prostaglandin transporter, SLCO2A1, mediates the invasion and apoptosis of lung cancer cells via PI3K/AKT/mTOR pathway. Int J Clin Exp Pathol 8:9175–9181PubMedPubMedCentral
Metadaten
Titel
Stress-triggered YAP1/SOX2 activation transcriptionally reprograms head and neck squamous cell carcinoma for the acquisition of stemness
verfasst von
Hirofumi Omori
Kuniaki Sato
Takafumi Nakano
Takahiro Wakasaki
Satoshi Toh
Kenichi Taguchi
Takashi Nakagawa
Muneyuki Masuda
Publikationsdatum
04.09.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 10/2019
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-019-02995-z

Weitere Artikel der Ausgabe 10/2019

Journal of Cancer Research and Clinical Oncology 10/2019 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.