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

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

研究成果: Contribution to journalArticle査読

2 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)2433-2444
ページ数12
ジャーナルJournal of Cancer Research and Clinical Oncology
145
10
DOI
出版ステータス出版済み - 10 1 2019
外部発表はい

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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