4.6 Article

HPRT promotes proliferation and metastasis in head and neck squamous cell carcinoma through direct interaction with STAT3

Journal

EXPERIMENTAL CELL RESEARCH
Volume 399, Issue 1, Pages -

Publisher

ELSEVIER INC
DOI: 10.1016/j.yexcr.2020.112424

Keywords

HPRT; EMT; EGFR inhibitor; STAT3; HNSCC

Funding

  1. National Natural Science Foundation of China [81772870]
  2. Health and Family Planning Commission Research Fund of Shanghai Municipality [201740186]
  3. Shanghai Pujiang Talents Program [15PJD024]
  4. Shanghai Summit & Plateau Disciplines, Clinical Diagnosis and Treatment Center Construction Project of Fengxian District [[2017]118]
  5. Science and Technology Development Fund of Shanghai Fengxian District Science and Technology Commission [20170702]

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A study showed that higher HPRT expression in HNSCC tissue is associated with poor prognosis, and overexpression of HPRT can increase the expression of EMT markers by interacting with STAT3. Knocking down HPRT significantly inhibits tumor growth and enhances the anticancer effect of EGFR inhibitors against HNSCC xenografts.
Increasing effort has been put into finding novel molecular pathways to improve the efficiency of EGFR inhibitors against head and neck squamous cell cancer (HNSCC). In this study, we performed data mining and bioinformatically analysed RNA-Seq data downloaded from TCGA and confirmed that higher expression of HPRT in HNSCC tissue was related to poor prognosis of patients. Then, we conducted in vitro and in vivo loss- and gain-of-function experiments to demonstrate the role of HPRT in HNSCC cell lines. Overexpression of HPRT increased the gene expression of epithelial mesenchymal transition markers via direct interaction with STAT3. Knocking down HPRT significantly decreased tumour growth and enhanced the anticancer effect of EGFR inhibitors against HNSCC xenografts. In conclusion, HPRT is a binding partner of STAT3 that promotes EMT and proliferation. Our findings support HPRT as a promising prognostic indicator and potential therapeutic target for HNSCC.

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