2. Academic Validation
  3. GATA3-NLRP1 Axis Inhibits Hepatocellular Carcinoma Progression Through the Hedgehog Signaling

GATA3-NLRP1 Axis Inhibits Hepatocellular Carcinoma Progression Through the Hedgehog Signaling

  • Cell Biol Int. 2026 Jan;50(1):e70116. doi: 10.1002/cbin.70116.
Dong Sun 1 2 3,  Xu Sun 2,  Jiazi Zhang 2,  Xiaofeng Wang 2,  Liqing Liu 2,  Jiaping Xie 3,  Hongli Song 1 4
Affiliations

Affiliations

  • 1 First Central Hospital of Tianjin Medical University, Tianjin, China.
  • 2 Department of Gastrointestinal Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
  • 3 Department of Gastroenterology, Liaocheng People's Hospital, Liaocheng, China.
  • 4 Department of Liver Transplantation, Tianjin First Central Hospital and Tianjin Key Laboratory of Organ Transplantation, Tianjin, China.
PMID: 41424411 DOI: 10.1002/cbin.70116
Abstract

As a member of the inflammasome, NLRP1 has been reported to play roles in some cancers. However, the effect of NLRP1 in hepatocellular carcinoma (HCC) remains elusive. This study aims to explore the effect and mechanism of NLRP1 on HCC. The effect of NLRP1 on HCC cell malignant behaviors was investigated by using CCK-8, EdU, colony formation, flow cytometry, wound healing and transwell invasion assays. The expression levels of relevant proteins were measured by western blot and immunohistochemical assay. In addition, tumor formation was detected using in vivo xenograft model in BALB/c nude mice. We discovered that NLRP1 was lowly expressed in HCC, and the increased NLRP1 expression was correlated with good prognosis in HCC patients. NLRP1 inhibited HCC cell proliferation, migration, invasion, epithelial-mesenchymal transition, and disrupted fatty acid metabolism. Moreover, NLRP1 knockdown reversed GATA3-mediated suppression of proliferation and migration in HCC cells. Besides, NLRP1 or GATA3 was demonstrated to inhibit HCC cell proliferation and migration via inhibiting Hedgehog signaling, which verified by the rescue experiments. Additionally, NLRP1 also inhibited tumor growth in nude mice. Our study demonstrated that GATA3-NLRP1 axis could inhibit proliferation, migration, and invasion of HCC cells, and disrupt fatty acid metabolism through suppressing Hedgehog signaling, highlighting the anti-cancer role of NLRP1 in HCC.

Keywords

GATA3; Hedgehog signaling; NLRP1; fatty acid metabolism; hepatocellular carcinoma.

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