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Elevated neuregulin‑1 expression modulates tumor malignancy and autophagy in esophageal squamous cell carcinoma

  • Authors:
    • Yen-Chiang Tseng
    • Pei-Feng Liu
    • Yu-Ru Chen
    • Wen-Hsin Yang
    • Chia-Che Chang
    • Hsueh-Wei Chang
    • Cheng-Hsin Lee
    • Yih-Gang Goan
    • Chih-Wen Shu
  • View Affiliations / Copyright

    Affiliations: Division of Thoracic Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 81341, Taiwan, R.O.C., Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80756, Taiwan, R.O.C., Institute of BioPharmaceutical Sciences, National Sun Yat‑sen University, Kaohsiung 80424, Taiwan, R.O.C., Department of Oncology, Zuoying Armed Forces General Hospital, Kaohsiung 81320, Taiwan, R.O.C.
    Copyright: © Tseng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 62
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    Published online on: February 12, 2025
       https://doi.org/10.3892/ijmm.2025.5503
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Abstract

The 5‑year survival rate of patients with esophageal squamous cell carcinoma (ESCC) is <20%, highlighting the need for the development of novel therapeutic targets. Neuregulin‑1 (NRG1), a transmembrane protein involved in cell proliferation and survival signaling, has unclear biological functions and clinical value in ESCC. The present study investigated the association between NRG1 expression and ESCC by analyzing data from both patients with ESCC and The Cancer Genome Atlas database. Reverse transcription‑quantitative PCR and immunohistochemistry staining were used to determine the levels of gene and protein in the tissue. The findings revealed that NRG1 gene and protein levels were significantly higher in tumor tissues compared with the normal tissues. Elevated expression of NRG1 was associated with poor outcomes, particularly in patients with advanced ESCC. Silencing NRG1 decreased both its mRNA and protein levels, disrupting key signaling pathways, such as phosphorylated (p‑)AKT and cellular rapidly accelerated fibrosarcoma (p‑cRAF), which led to decreased cancer cell proliferation, migration and tumor sphere formation, along with increased cell death. High expression levels of NRG1 and cRAF were significantly associated with poor prognosis. Additionally, silencing NRG1 promoted autophagosome and autolysosome formation, decreasing LC3B levels. The use of the autophagy inhibitor chloroquine significantly enhanced cell death induced by NRG1 silencing, suggesting that autophagy functions as a survival mechanism in ESCC cells in which NRG1 is silenced. Furthermore, high co‑expression of NRG1 and LC3B was associated with a worse prognosis. On the whole, the present study demonstrated that targeting NRG1 with autophagy inhibitors may serve as a potential therapeutic strategy for ESCC.
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Copy and paste a formatted citation
Spandidos Publications style
Tseng Y, Liu P, Chen Y, Yang W, Chang C, Chang H, Lee C, Goan Y and Shu C: Elevated neuregulin‑1 expression modulates tumor malignancy and autophagy in esophageal squamous cell carcinoma. Int J Mol Med 55: 62, 2025.
APA
Tseng, Y., Liu, P., Chen, Y., Yang, W., Chang, C., Chang, H. ... Shu, C. (2025). Elevated neuregulin‑1 expression modulates tumor malignancy and autophagy in esophageal squamous cell carcinoma. International Journal of Molecular Medicine, 55, 62. https://doi.org/10.3892/ijmm.2025.5503
MLA
Tseng, Y., Liu, P., Chen, Y., Yang, W., Chang, C., Chang, H., Lee, C., Goan, Y., Shu, C."Elevated neuregulin‑1 expression modulates tumor malignancy and autophagy in esophageal squamous cell carcinoma". International Journal of Molecular Medicine 55.4 (2025): 62.
Chicago
Tseng, Y., Liu, P., Chen, Y., Yang, W., Chang, C., Chang, H., Lee, C., Goan, Y., Shu, C."Elevated neuregulin‑1 expression modulates tumor malignancy and autophagy in esophageal squamous cell carcinoma". International Journal of Molecular Medicine 55, no. 4 (2025): 62. https://doi.org/10.3892/ijmm.2025.5503
Copy and paste a formatted citation
x
Spandidos Publications style
Tseng Y, Liu P, Chen Y, Yang W, Chang C, Chang H, Lee C, Goan Y and Shu C: Elevated neuregulin‑1 expression modulates tumor malignancy and autophagy in esophageal squamous cell carcinoma. Int J Mol Med 55: 62, 2025.
APA
Tseng, Y., Liu, P., Chen, Y., Yang, W., Chang, C., Chang, H. ... Shu, C. (2025). Elevated neuregulin‑1 expression modulates tumor malignancy and autophagy in esophageal squamous cell carcinoma. International Journal of Molecular Medicine, 55, 62. https://doi.org/10.3892/ijmm.2025.5503
MLA
Tseng, Y., Liu, P., Chen, Y., Yang, W., Chang, C., Chang, H., Lee, C., Goan, Y., Shu, C."Elevated neuregulin‑1 expression modulates tumor malignancy and autophagy in esophageal squamous cell carcinoma". International Journal of Molecular Medicine 55.4 (2025): 62.
Chicago
Tseng, Y., Liu, P., Chen, Y., Yang, W., Chang, C., Chang, H., Lee, C., Goan, Y., Shu, C."Elevated neuregulin‑1 expression modulates tumor malignancy and autophagy in esophageal squamous cell carcinoma". International Journal of Molecular Medicine 55, no. 4 (2025): 62. https://doi.org/10.3892/ijmm.2025.5503
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