ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2016
Sonic hedgehog signaling pathway mediates development of hepatocellular carcinoma.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Fibrosis and Hepatocarcinogenesis: Role of Gene-Environment Interactions in Liver Disease Progression.International journal of molecular sciences · 2024Review
- Signaling pathways in liver cancer: pathogenesis and targeted therapy.Molecular biomedicine · 2024Review
- Reappraisal of the Roles of the Sonic Hedgehog Signaling Pathway in Hepatocellular Carcinoma.Cancers · 2024Review
- Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies.Signal transduction and targeted therapy · 2023Review
- Review
- Downregulation of Sonic hedgehog signaling induces G2-arrest in genital warts.Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) · 2023Article
- Long Non-Coding RNA Expression Profile Alteration Induced by Titanium Dioxide Nanoparticles in HepG2 Cells.Toxics · 2022Article
- Sonic Hedgehog signaling pathway in gynecological and genitourinary cancer (Review).International journal of molecular medicine · 2021Review
- Targeting Liver Cancer Stem Cells: An Alternative Therapeutic Approach for Liver Cancer.Cancers · 2020Review
- The Role of Smoothened in Cancer.International journal of molecular sciences · 2020Review
- Sonic Hedgehog Signaling in Organogenesis, Tumors, and Tumor Microenvironments.International journal of molecular sciences · 2020Review
- Sonic Hedgehog signaling pathway as a potential target to inhibit the progression of hepatocellular carcinoma.Oncology letters · 2019Review
- Keratin 23 Is a Peroxisome Proliferator-Activated Receptor Alpha-Dependent, MYC-Amplified Oncogene That Promotes Hepatocyte Proliferation.Hepatology (Baltimore, Md.) · 2019Article
- The expressions of Hedgehog and PI3K-AKT pathway components correlate with invasion and metastasis in hepatocellular carcinoma.International journal of clinical and experimental pathology · 2019Article
- Molecular pathways of nonalcoholic fatty liver disease development and progression.Cellular and molecular life sciences : CMLS · 2019Review
- Identification of key genes and pathways by bioinformatics analysis with TCGA RNA sequencing data in hepatocellular carcinoma.Molecular and clinical oncology · 2018Article
- Dihydroartemisinin induces apoptosis and inhibits proliferation, migration, and invasion in epithelial ovarian cancer via inhibition of the hedgehog signaling pathway.Cancer medicine · 2018Article
- The hedgehog pathway in nonalcoholic fatty liver disease.Critical reviews in biochemistry and molecular biology · 2018Review
- Extracephalic manifestations of nonchromosomal, nonsyndromic holoprosencephaly.American journal of medical genetics. Part C, Seminars in medical genetics · 2018Review
- CCL2/CCR2 axis induces hepatocellular carcinoma invasion and epithelial-mesenchymal transition in vitro through activation of the Hedgehog pathway.Oncology reports · 2018Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although abnormal activation of the sonic hedgehog (Shh) signaling pathway has been demonstrated in human hepatocellular carcinoma (HCC) patients and in most HCC cell lines, the mechanism by which the Shh pathway promotes the development of HCC remains uncertain. Using a liver cancer model induced by diethylnitrosamine (DEN) which mimics the process from liver injury, abnormal hepatocyte proliferation, and hepatocirrhosis to hepatocyte canceration, we investigated the abnormal activation of the Shh pathway by examining the expression of Shh, patched-1 (Ptch), smoothened (SMO), and glioma-associated oncogene-1 (Gli1) genes. During this process, the expression of CDK1 and cyclin B1 protein, which are two components of the M-phase promoting factor (MPF) controlling G2/M transition, was also examined to explore the potential relationship between Shh activation and cell cycle progression. We observed that the cells with Shh, Ptch, and Gli1 protein expression were mainly distributed in hyperplastic nodule, cancerous node, the epithelia of interlobular bile duct, and precancerous tissues. A gradually increasing tendency of the positive expression rate of Shh, Ptch, and Gli1 proteins in the process from the beginning normal tissue to the final cancer formation was revealed. The cyclin B1 and CDK1 expression level was higher in the DEN-induced rats as compared with normal rats, and their expression was mainly distributed in the portal area of the liver, hyperplastic nodule, cancerous node, and precancerous tissues. Our results suggested that the Shh signaling pathway is activated during liver carcinogenesis, and activated Shh signaling promotes the cell proliferation by facilitating the G2/M transition through increasing the expression of cyclin B1 and CDK1 protein, which eventually results in the development of liver cancer. Better understanding of the Shh signaling pathway in HCC may contribute to the development of novel therapeutic strategies in inhibiting cell proliferation and promoting cell cycle arrest.
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