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

Lin Wang; Yupu Wang; Nannan Han; Xu Wang; Min Ruan

doi:10.1016/j.yexcr.2020.112424

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

Exp Cell Res. 2021 Feb 1;399(1):112424. doi: 10.1016/j.yexcr.2020.112424. Epub 2020 Dec 21.

Authors

Lin Wang¹, Yupu Wang¹, Nannan Han¹, Xu Wang², Min Ruan³

Affiliations

¹ Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200011, China; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, China; National Clinical Research Center for Oral Disease, Shanghai, 200011, China.
² Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200011, China; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, China; National Clinical Research Center for Oral Disease, Shanghai, 200011, China. Electronic address: [email protected].
³ Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200011, China; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, China; National Clinical Research Center for Oral Disease, Shanghai, 200011, China. Electronic address: [email protected].

PMID: 33340493
DOI: 10.1016/j.yexcr.2020.112424

Abstract

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.

Keywords: EGFR inhibitor; EMT; HNSCC; HPRT; STAT3.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Movement / genetics
Cell Proliferation / genetics
Epithelial-Mesenchymal Transition / genetics
Epithelial-Mesenchymal Transition / physiology
Head and Neck Neoplasms / genetics
Head and Neck Neoplasms / metabolism
Head and Neck Neoplasms / pathology*
Humans
Hypoxanthine Phosphoribosyltransferase / genetics
Hypoxanthine Phosphoribosyltransferase / metabolism
Hypoxanthine Phosphoribosyltransferase / physiology*
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasm Metastasis
Protein Binding
STAT3 Transcription Factor / metabolism*
Squamous Cell Carcinoma of Head and Neck / genetics
Squamous Cell Carcinoma of Head and Neck / metabolism
Squamous Cell Carcinoma of Head and Neck / pathology*
Tumor Cells, Cultured

Substances

STAT3 Transcription Factor
STAT3 protein, human
Hypoxanthine Phosphoribosyltransferase