Chromogranin B promotes EMT-associated stem-like properties and chemoresistance in HNSCC
4 affiliations
- 1Department of Otorhinolaryngology Head and Neck Surgery, Chongqing General Hospital, Chongqing Academy of Medical Sciences, Chongqing University, Chongqing, China
- 2Key Laboratory of Hearing and Speech Cognition (Municipal Health Commission), Chongqing, China
- 3College of Pharmacy, Chongqing Medical University, Chongqing, China
- 4Department of Otorhinolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Abstract
Background: Epithelial–mesenchymal transition (EMT)-associated stemness and therapeutic resistance are major drivers of HNSCC progression; however, the upstream regulators coordinating these malignant programs remain incompletely understood.
Methods: TCGA-HNSC, GEO, and single-cell RNA sequencing datasets were analyzed to evaluate CHGB expression, prognostic value, and its association with epithelial–mesenchymal transition (EMT). EMT scoring, gene set enrichment analysis, weighted gene co-expression network analysis, and Cox regression analyses were performed. Gain- and loss-of-function approaches, xenograft models, tumorsphere formation assays, cisplatin sensitivity assays, and rescue experiments were used to investigate the biological functions and molecular mechanisms of CHGB in HNSCC.
Result: CHGB was significantly upregulated in HNSCC tissues and associated with poor overall survival. Integrative analyses identified a strong association between CHGB expression and EMT-related transcriptional programs. Functionally, CHGB depletion inhibited proliferation, migration, cell-cycle progression, primary and secondary tumorsphere formation, cisplatin resistance in vitro, and tumor growth in vivo, whereas CHGB overexpression exerted opposite effects. Mechanistically, CHGB promoted EMT-associated stemness and chemoresistance by sustaining ZEB1 expression through PI3K/AKT signaling. ZEB1 restoration partially rescued the impaired self-renewal capacity and enhanced cisplatin sensitivity induced by CHGB knockdown, whereas ZEB1 silencing attenuated CHGB-driven malignant phenotypes. Single-cell transcriptomic analyses further confirmed that CHGB was enriched in malignant cells and positively associated with EMT and stemness programs.
Conclusions: CHGB functions as a critical regulator of EMT-associated stemness and chemoresistance through the PI3K/AKT/ZEB1 axis and represents a potential prognostic biomarker and therapeutic target in HNSCC.
Graphical Abstract:
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12967-026-08729-3.
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BibTeX
@article{li2026chromogranin,
title = {{Chromogranin B promotes EMT-associated stem-like properties and chemoresistance in HNSCC}},
author = {Zhongwan Li and Lie Yuan and Yu Jiang and Xian Li and Fan Li and Lifeng Jia and Xiaoli Li and Wei Yuan and Yucheng Yang and Shitong Zhou},
journal = {Journal of Translational Medicine},
year = {2026},
month = jul,
doi = {10.1186/s12967-026-08729-3},
url = {https://doi.org/10.1186/s12967-026-08729-3},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Chromogranin B promotes EMT-associated stem-like properties and chemoresistance in HNSCC
AU - Zhongwan Li
AU - Lie Yuan
AU - Yu Jiang
AU - Xian Li
AU - Fan Li
AU - Lifeng Jia
AU - Xiaoli Li
AU - Wei Yuan
AU - Yucheng Yang
AU - Shitong Zhou
PY - 2026
DA - 2026/07/01
JO - Journal of Translational Medicine
DO - 10.1186/s12967-026-08729-3
UR - https://doi.org/10.1186/s12967-026-08729-3
AB - Background: Epithelial–mesenchymal transition (EMT)-associated stemness and therapeutic resistance are major drivers of HNSCC progression; however, the upstream regulators coordinating these malignant programs remain incompletely understood. Methods: TCGA-HNSC, GEO, and single-cell RNA sequencing datasets were analyzed to evaluate CHGB expression, prognostic value, and its association with epithelial–mesenchymal transition (EMT). EMT scoring, gene set enrichment analysis, weighted gene co-expression network analysis, and Cox regression analyses were performed. Gain- and loss-of-function approaches, xenograft models, tumorsphere formation assays, cisplatin sensitivity assays, and rescue experiments were used to investigate the biological functions and molecular mechanisms of CHGB in HNSCC. Result: CHGB was significantly upregulated in HNSCC tissues and associated with poor overall survival. Integrative analyses identified a strong association between CHGB expression and EMT-related transcriptional programs. Functionally, CHGB depletion inhibited proliferation, migration, cell-cycle progression, primary and secondary tumorsphere formation, cisplatin resistance in vitro, and tumor growth in vivo, whereas CHGB overexpression exerted opposite effects. Mechanistically, CHGB promoted EMT-associated stemness and chemoresistance by sustaining ZEB1 expression through PI3K/AKT signaling. ZEB1 restoration partially rescued the impaired self-renewal capacity and enhanced cisplatin sensitivity induced by CHGB knockdown, whereas ZEB1 silencing attenuated CHGB-driven malignant phenotypes. Single-cell transcriptomic analyses further confirmed that CHGB was enriched in malignant cells and positively associated with EMT and stemness programs. Conclusions: CHGB functions as a critical regulator of EMT-associated stemness and chemoresistance through the PI3K/AKT/ZEB1 axis and represents a potential prognostic biomarker and therapeutic target in HNSCC. Graphical Abstract: Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12967-026-08729-3.
SN - 1479-5876
ER -