ArticleCell death & disease2024
SPINK13 acts as a tumor suppressor in hepatocellular carcinoma by inhibiting Akt phosphorylation.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Targeting the Notch signaling pathway in digestive system cancers: from bench to bedside.Cancer cell international · 2026Review
- SPINK2 in hematopoiesis and cancer: Biology and clinical implications.Cell death discovery · 2026Review
- The SPINK Protein Family in Cancer: Emerging Roles in Tumor Progression, Therapeutic Resistance, and Precision Oncology.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Study on effect of pancreatic kininogenase on diabetic nephropathy-induced fibrosis via Notch1/Hes1/Pten/Akt signaling pathway.BMC nephrology · 2025Article
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Authors and funding
7 authors.
Funding
Abstract
The PI3K/Akt pathway is overexpressed in nearly 50% of hepatocellular carcinomas and inhibits apoptosis by promoting the expression of antiapoptotic genes. Serine protease inhibitors have been shown to induce apoptosis in hepatoma cells by downregulating SPINK13 in the PI3K/Akt pathway. In this study, SPINK13 was expressed in lentiviral vectors. Changes in signaling pathway adapter proteins, apoptosis regulatory proteins, cell cycle regulatory proteins, and the biological behavior of hepatocellular carcinoma were observed in cell and nude mouse xenograft models. The underlying mechanism of endogenous SPINK13-induced apoptosis in hepatocellular carcinoma cells was explored via transcriptomics. As a result, endogenous SPINK13 might inhibit the activity of Furin protease, downregulate the Notch1/Hes1 pathway in a binding manner, activate the direct effector PTEN, inhibit Akt phosphorylation, inactivate the downstream PI3K/Akt pathway, and ultimately lead to mitochondrial apoptosis and cell cycle arrest in hepatoma cells. Therefore, the Notch1/Hes1/PTEN pathway may act upstream of SPINK13 to downregulate the PI3K/Akt signaling pathway. Our study helps elucidate the underlying mechanism of SPINK13 in anti-hepatocellular carcinoma and lays a theoretical foundation for the development of novel therapeutic serine protease inhibitors.
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