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2021 Fiscal Year Final Research Report

Investigation of transcriptional reprogramming mechanisms involved in invasion and metastasis of head and neck squamous cell caricnoma

Research Project

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Project/Area Number 20K18300
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56050:Otorhinolaryngology-related
Research InstitutionNational Hospital Organization, Kyushu Cancer Center

Principal Investigator

Sato Kuniaki  独立行政法人国立病院機構(九州がんセンター臨床研究センター), その他部局等, 頭頸科医師 (10859622)

Project Period (FY) 2020-04-01 – 2022-03-31
Keywords頭頸部癌 / 扁平上皮癌 / バイオインフォマティクス / エピジェネティクス / RNAシーケンシング / ChIPシーケンシング
Outline of Final Research Achievements

To reveal the transcriptional reprogramming mechanisms which contribute to the progression and evolution of head and neck squamous cell carcinoma (HNSCC), we performed multi-omics analysis using surgically-resected primary tumors, lymph node metastasis and non-cancerous tissue samples of HNSCC patients. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) followed by bioinformatics analysis indicated that transcriptional co-factor Yes-associated protein 1 (YAP1) and transcription factor Paired-like homeodomein 2 (PITX2) cooperatively induce transcriptional reprogramming in HNSCC. Immunohistochemical staining of YAP1 and PITX2 in primary HNSCC tissues showed that both YAP1 and PITX2 predict poor prognosis of HNSCC patients. Furthermore, knockdown of PITX2 significantly reduced proliferation abilities of HNSCC-derived cells. Further analyses are needed to conclude our findings and to develop novel therapeutic strategies targeting YAP1/PITX2 in HNSCC.

Free Research Field

耳鼻咽喉科

Academic Significance and Societal Importance of the Research Achievements

頭頸部癌の遺伝子変異はTP53などがん抑制遺伝子の機能喪失変異が主体であり、直接の治療標的となり得る遺伝子異常がほとんどない。これに対し我々は、頭頸部癌は転写リプログラミング機構に強く依存する悪性腫瘍であると仮説を立てた。今回、実際の頭頸部癌患者から得られた検体を用いたマルチオミクス解析によりYAP1とPITX2が協調して転写リプログラミング機構に関与する可能性を示した。本研究のような臨床検体を用いた頭頸部癌のマルチオミクス解析は前例がなく、学術的意義が高いと考えられる。また、本研究成果によりYAP1/PITX2が治療標的となる可能性が示唆され、今後の頭頸部癌治療の発展に繋がると期待される。

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Published: 2023-01-30  

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