NRG1 promotes tumorigenesis and metastasis and afatinib treatment efficiency is enhanced by NRG1 inhibition in esophageal squamous cell carcinoma

• Published in: Biochemical pharmacology 2023-12, Vol.218, p.115920-115920, Article 115920
• Main Authors: Hou, Guiqin, Niu, Tengda, Jia, Ang, Zhang, Yingying, Chen, Xunan, Wei, Huiyun, Jia, Yilin, Xu, Yichao, Li, Yan, Wang, Pengju, Chatterjee, Aniruddha
• Format: Article
• Language: English
• Subjects: Afatinib; Carcinogenesis - genetics; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Transformation, Neoplastic; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - genetics; Esophageal squamous cell carcinoma; Esophageal Squamous Cell Carcinoma - drug therapy; Gene Expression Regulation, Neoplastic; Humans; Migration; MMP9; Neuregulin-1 - genetics; Neuregulin-1 - metabolism; NF-κB; NRG1
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2023.115920

This study found NRG1 upregulation in esophageal cancer due to gene amplification, promoting tumor growth and metastasis. Afatinib inhibits NRG1-overexpressed ESCC effectively. [Display omitted] Esophageal squamous cell carcinoma (ESCC) is a highly aggressive tumor with significant heterogeneity in incidence and outcomes. The role of Neuregulin 1 (NRG1) in ESCC and its contribution to aggressiveness remain unknown. This study aims to investigate the functions and molecular mechanisms of NRG1 in ESCC as well as the treatment strategy for ESCC with overexpression of NRG1. We firstly demonstrated the upregulation of NRG1 and a negative correlation trend between patients' overall survival (OS) and the expression level of NRG1 in esophageal cancer. And then we found NRG1 promoted cell proliferation, migration, inhibited apoptosis, and accelerated tumorigenesis and metastasis in ESCC using cell lines and xenograft models. Furthermore, we discovered that NRG1 activated the NF-κB/MMP9 signaling pathway, contributing to the metastatic phenotype in ESCC. Finally, we show that afatinib (FDA approved cancer growth blocker) could inhibit ESCC with overexpressed NRG1 and down-regulation of NRG1 along with afatinib treatment provides higher efficient strategy. This study uncovers the critical role and molecular mechanism of NRG1 in ESCC tumorigenesis and metastasis, suggesting its potential as a novel biomarker for ESCC treatment.