Related Experiment Video
Updated: Aug 7, 2026
Study of Viral Vectors in a Three-dimensional Liver Model Repopulated with the Human Hepatocellular Carcinoma Cell Line HepG2
Published on: October 24, 2016
Reduced expression of CYLD in human colon and hepatocellular carcinomas
Claus Hellerbrand1, Elisabeth Bumes, Frauke Bataille
1Department of Internal Medicine I, University Regensburg, 93053 Regensburg, Germany. claus.hellerbrand@klinik.uni-regensburg.de
Abstract:
CYLD was originally identified as a tumor suppressor that is mutated in familial cylindromatosis. Recent studies suggested a role for CYLD in nuclear factor-kappaB (NF-kappaB) regulation. NF-kappaB activation has been connected with multiple aspects of oncogenesis but the underlying molecular mechanisms of persistent NF-kappaB activation in tumors remain largely unknown. Thus, we evaluated CYLD transcription in different colon and hepatocellular carcinoma cell lines and tissue samples, respectively. CYLD was downregulated or lost in all tumor cell lines investigated as compared with primary human colonic epithelial cells and hepatocytes, respectively. Further, quantitative PCR analysis revealed reduced CYLD mRNA expression in most tumor samples compared with non-tumorous tissue. Analysis on protein level confirmed these findings. Functional assays with CYLD transfected cell lines revealed that CYLD expression decreased NF-kappaB activity. Thus, functional relevant loss of CYLD expression may contribute to tumor development and progression, and may provide a new target for therapeutic strategies.
Insights
Loss of the CYLD tumor suppressor gene is linked to increased nuclear factor-kappaB (NF-kappaB) activity, promoting cancer development. Restoring CYLD may offer new therapeutic strategies for colon and liver cancers.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- CYLD is a known tumor suppressor gene linked to familial cylindromatosis.
- Recent research implicates CYLD in the regulation of nuclear factor-kappaB (NF-kappaB) signaling.
- Persistent NF-kappaB activation is a hallmark of oncogenesis, but its mechanisms in tumors are not fully understood.
Purpose of the Study:
- To investigate the role of CYLD in NF-kappaB regulation in cancer.
- To evaluate CYLD expression levels in colon and hepatocellular carcinoma cell lines and tissues.
Main Methods:
- Quantitative PCR (qPCR) to assess CYLD mRNA expression.
- Western blot analysis to confirm protein levels.
- Functional assays involving CYLD transfection in cancer cell lines.
Main Results:
- CYLD was downregulated or completely lost in colon and hepatocellular carcinoma cell lines compared to normal cells.
- Reduced CYLD mRNA and protein expression were observed in most tumor samples versus non-tumorous tissues.
- Transfection with CYLD decreased NF-kappaB activity in cancer cells.
Conclusions:
- Functional loss of CYLD expression contributes to tumor development and progression.
- CYLD's role in suppressing NF-kappaB activity suggests it as a potential therapeutic target for cancers.