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Reduced expression of TANGO in colon and hepatocellular carcinomas
Stephanie Arndt1, Anja K Bosserhoff
1Institute of Pathology, University of Regensburg, D-93053 Regensburg, Germany.
Abstract:
The TANGO gene was originally identified as a new family member of the MIA gene family. The gene codes for a 14-kDa protein of so far unknown function. Recently, we identified TANGO as a tumor suppressor in malignant melanoma. In this study we evaluated TANGO transcription in different colon and hepatocellular carcinoma cell lines and tissue samples, to analyze whether loss of TANGO expression is a more general process in tumor development. TANGO was down-regulated or lost in all hepatocellular and colon cell lines compared to primary human hepatocytes or normal colon epithelial cells, respectively, and in most of the tumor samples compared to non-tumorous tissue. These results were confirmed in situ by immunohistochemistry on paraffin-embedded sections of colon and hepatocellular tumors. Functional assays with exogenous TANGO treatment of colon and hepatoma cell lines revealed reduced motility and invasion capacity. Our studies present for the first time the down-regulation of TANGO in colon and hepatocellular carcinoma and provide the first indications for a tumor suppressor role of the TANGO gene in human colon and hepatocellular carcinoma. Thus, functional relevant loss of TANGO expression may contribute to general tumor development and progression, and may provide a new target for therapeutic strategies.
Insights
The TANGO gene shows reduced expression in colon and liver cancers. This suggests TANGO acts as a tumor suppressor, potentially offering new therapeutic targets for these cancers.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The TANGO gene, a member of the MIA gene family, encodes a protein of unknown function.
- TANGO was recently identified as a tumor suppressor in malignant melanoma.
- The role of TANGO in other major human cancers remains unexplored.
Purpose of the Study:
- To investigate TANGO gene transcription in colon and hepatocellular carcinoma.
- To determine if TANGO down-regulation is a common event in tumor development.
- To explore the functional impact of TANGO loss in cancer progression.
Main Methods:
- Analysis of TANGO gene expression in various colon and hepatocellular carcinoma cell lines and patient tissue samples.
- In situ confirmation using immunohistochemistry on tumor sections.
- Functional assays assessing cell motility and invasion after TANGO reintroduction.
Main Results:
- TANGO expression was significantly down-regulated or lost in all tested colon and hepatocellular carcinoma cell lines.
- Reduced TANGO expression was observed in most tumor samples compared to non-tumorous tissues.
- Restoring TANGO expression in cancer cells reduced their motility and invasion capacity.
Conclusions:
- TANGO gene down-regulation is a frequent event in colon and hepatocellular carcinoma.
- These findings provide the first evidence for a tumor suppressor role of TANGO in these cancers.
- Loss of TANGO function may contribute to tumor development and progression, identifying it as a potential therapeutic target.