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Galectin-4 functions as a tumor suppressor of human colorectal cancer
Arun Satelli1, Prema S Rao, Seshadri Thirumala
1Department of Biomedical Sciences, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA.
Abstract:
Development of colorectal cancer (CRC) involves a series of genetic alterations with altered expression of proteins and cell signaling pathways. Here, we identified that galectin-4 (gal-4), a marker of differentiation, was down-regulated in CRC. The goal of this work was to determine the function of gal-4 in CRC. Toward this goal, the human colon biopsies and tissue microarrays containing a gradient of pathology were analyzed for gal-4 expression by immunohistochemistry. Cell proliferation, migration, motility, forced expression, knockdown, cell cycle and apoptosis assays were used to characterize gal-4 function. Immunohistochemistry identified that gal-4 expression was significantly down-regulated in adenomas and was essentially absent in invasive carcinomas. Forced expression of gal-4 in gal-4 -ve cells induced cell cycle arrest and retarded cell migration and motility. Further, gal-4 sensitized the cells to camptothecin-induced apoptosis. Gal-4 knockdown resulted in increased cell proliferation, migration and motility. Gal-4 was found to be associated with Wnt signaling proteins. Finally, gal-4 expression led to down-regulation of Wnt signaling target genes. This study demonstrates that loss of gal-4 is a common and specific event in CRC. This study also shows that gal-4 exhibits tumor suppressive effects in CRC cells in vitro. Through its ability to interact with and down-regulate the functions of Wnt signaling pathway, gal-4 reveals a new dimension in the control of the Wnt signaling pathway. Thus, gal-4 may prove to be an important molecule in understanding the biology of CRC.
Insights
Loss of galectin-4 (gal-4), a differentiation marker, is common in colorectal cancer (CRC). Restoring gal-4 suppresses tumor growth, migration, and Wnt signaling, indicating its tumor-suppressive role in CRC development.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Colorectal cancer (CRC) development involves genetic alterations affecting protein expression and cell signaling.
- Galectin-4 (gal-4), a differentiation marker, is observed to be downregulated in CRC.
- Understanding the functional role of gal-4 in CRC is crucial for targeted therapies.
Purpose of the Study:
- To investigate the functional significance of galectin-4 (gal-4) in colorectal cancer (CRC).
- To determine the impact of gal-4 expression levels on CRC cell behavior and signaling pathways.
Main Methods:
- Immunohistochemistry on human colon biopsies and tissue microarrays to assess gal-4 expression.
- In vitro assays including cell proliferation, migration, motility, cell cycle, and apoptosis.
- Gal-4 forced expression and knockdown studies.
- Analysis of Wnt signaling pathway interactions and target gene expression.
Main Results:
- Galectin-4 (gal-4) expression was significantly reduced in adenomas and absent in invasive colorectal carcinomas (CRCs).
- Forced gal-4 expression in gal-4-negative CRC cells induced cell cycle arrest, reduced migration and motility, and enhanced apoptosis.
- Gal-4 knockdown increased CRC cell proliferation, migration, and motility.
- Gal-4 interacts with Wnt signaling proteins, leading to the downregulation of Wnt signaling target genes.
Conclusions:
- Loss of galectin-4 (gal-4) is a frequent and specific event in colorectal cancer (CRC) development.
- Gal-4 exhibits tumor-suppressive properties in CRC cells by inhibiting proliferation, migration, and motility.
- Gal-4 negatively regulates the Wnt signaling pathway, offering a novel therapeutic target for CRC.
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