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Peer-reviewedCC BYInternational journal of biological sciences

FKBP9 Drives Hepatocellular Carcinoma EMT by Regulating SEPT6 Transcription and Stability to Activate TGF-β Signaling.

  • Yu Zhang1,2
  • Rixin Su1,2
  • Jie Zou3
  • Wangyang Sun1,2
  • Banglong Song1,2
  • Long Liu4,5
  • Shuanghu Yuan1,2
5 affiliations
  1. 1Department of Radiation Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
  2. 2Department of Radiation Oncology, Anhui Provincial Cancer Hospital, Hefei, Anhui, 230031, China.
  3. 3Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230001, China.
  4. 4Department of Surgery, University of Pennsylvania Perelman School of Medicine, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA.
  5. 5Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, China.
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Abstract

Epithelial-mesenchymal transition (EMT) drives hepatocellular carcinoma (HCC) progression, yet key EMT-driving genes specifically acting in malignant epithelial subpopulations remain poorly characterized. Here, we systematically screened EMT-related genes with cancer cell-specific high expression in HCC, and investigated the functional roles and downstream mechanisms of FKBP9. We found that FKBP9 was specifically highly expressed in HCC cancer cell subpopulations, and functionally promoted HCC cell proliferation, clonogenicity, migration and EMT progression. Mechanistically, FKBP9 enhanced SEPT6 transcription by upregulating c-MYC, and directly bound to SEPT6 protein to increase its stability, which in turn activated the TGF-β1 signaling cascade to drive EMT. We further validated the preclinical anti-HCC efficacy of pinyonomycin as a putative FKBP9-targeting inhibitor. Our findings indicate that FKBP9 drives HCC progression and EMT via the SEPT6-mediated TGF-β pathway, highlighting FKBP9 as a promising therapeutic target for HCC.

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Cite

BibTeXRIS
BibTeX
@article{zhang2026fkbp9,
  title = {{FKBP9 Drives Hepatocellular Carcinoma EMT by Regulating SEPT6 Transcription and Stability to Activate TGF-β Signaling.}},
  author = {Yu Zhang and Rixin Su and Jie Zou and Wangyang Sun and Banglong Song and Long Liu and Shuanghu Yuan},
  journal = {International journal of biological sciences},
  year = {2026},
  month = sep,
  doi = {10.7150/ijbs.134156},
  url = {https://europepmc.org/article/MED/42909909},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - FKBP9 Drives Hepatocellular Carcinoma EMT by Regulating SEPT6 Transcription and Stability to Activate TGF-β Signaling.
AU  - Yu Zhang
AU  - Rixin Su
AU  - Jie Zou
AU  - Wangyang Sun
AU  - Banglong Song
AU  - Long Liu
AU  - Shuanghu Yuan
PY  - 2026
DA  - 2026/09/11
JO  - International journal of biological sciences
DO  - 10.7150/ijbs.134156
UR  - https://europepmc.org/article/MED/42909909
AB  - Epithelial-mesenchymal transition (EMT) drives hepatocellular carcinoma (HCC) progression, yet key EMT-driving genes specifically acting in malignant epithelial subpopulations remain poorly characterized. Here, we systematically screened EMT-related genes with cancer cell-specific high expression in HCC, and investigated the functional roles and downstream mechanisms of FKBP9. We found that FKBP9 was specifically highly expressed in HCC cancer cell subpopulations, and functionally promoted HCC cell proliferation, clonogenicity, migration and EMT progression. Mechanistically, FKBP9 enhanced SEPT6 transcription by upregulating c-MYC, and directly bound to SEPT6 protein to increase its stability, which in turn activated the TGF-β1 signaling cascade to drive EMT. We further validated the preclinical anti-HCC efficacy of pinyonomycin as a putative FKBP9-targeting inhibitor. Our findings indicate that FKBP9 drives HCC progression and EMT via the SEPT6-mediated TGF-β pathway, highlighting FKBP9 as a promising therapeutic target for HCC.
SN  - 1449-2288
ER  -