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Epidermal Growth Factor Downregulates Carbon Anhydrase III (CAIII) in Colon Cancer
1Department of Veterinary Medicine, Susurluk Agriculture and Forestry Vocational School, Bandırma Onyedi Eylül University, Susurluk 10600, Balıkesir, Türkiye.
Abstract:
Colorectal cancer (CRC) is the second leading cause of cancer-related death in the world. Dysregulations in the EGF signaling pathway have been associated with colon cancer. Some members of the carbonic anhydrase family serve as biomarkers in cancer. Carbonic anhydrase III (CAIII), a member of this family, shows different activities than the other members of its family and has been associated with cancer. However, there are no studies on the effective regulation of EGF. In this study, we investigated the EGF-influenced regulation of CAIII in the HT29, SW480, and HUVEC cell lines and showed that CAIII regulation decreased with the effect of EGF. We aimed to investigate the EGF-affected mRNA and protein regulation of the CAIII gene in HT29, SW480, and HUVEC cell lines. For this purpose, we determined time-dependent CAIII mRNA and protein expression by applying EGF to HT29, SW480, and HUVEC cells. Time-dependent EGF-induced mRNA and protein level regulation of the CAIII gene decreased in the HT29, SW480, and HUVEC cell lines. EGF regulates the motility, adhesion, and metastasis of cancer cells. CAIII prevents cells from metastasizing through cell acidification. Therefore, our findings explained why the EGF-effective regulation of CAIII decreased. We suggest that the CAIII gene is promising as a targeted therapy due to the decrease in EGF-effected CAIII gene regulation in colon carcinoma.
Insights
Epidermal Growth Factor (EGF) signaling impacts carbonic anhydrase III (CAIII) gene expression in colorectal cancer cells. This study found EGF decreases CAIII levels, suggesting CAIII as a potential target for colon cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide.
- Epidermal Growth Factor (EGF) signaling pathways are implicated in colon cancer development.
- Carbonic anhydrase III (CAIII) is a potential cancer biomarker, but its regulation by EGF is unstudied.
Purpose of the Study:
- To investigate the effect of EGF on the regulation of CAIII mRNA and protein expression.
- To explore the role of EGF-mediated CAIII regulation in cancer cell behavior.
- To assess the therapeutic potential of targeting CAIII in colon carcinoma.
Main Methods:
- Utilized HT29, SW480, and HUVEC cell lines.
- Administered EGF to cell cultures to observe its effects.
- Quantified time-dependent changes in CAIII mRNA and protein expression levels.
Main Results:
- EGF exposure led to a time-dependent decrease in CAIII mRNA and protein levels in all tested cell lines.
- Observed reduction in CAIII expression correlated with EGF's known effects on cancer cell motility, adhesion, and metastasis.
- CAIII's role in preventing metastasis via cell acidification provides a mechanistic link to the observed EGF effect.
Conclusions:
- EGF signaling negatively regulates CAIII expression in colorectal cancer cells.
- The decrease in CAIII under EGF influence may contribute to cancer cell metastasis.
- CAIII represents a promising therapeutic target for colon carcinoma, particularly in contexts of dysregulated EGF signaling.
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