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AKAP4 mediated tumor malignancy in esophageal cancer
Shujun Li1, Xuebo Qin2, Yanjie Li3
1Department of Thoracic Surgery, The Second Hospital of Hebei Medical University Shijiazhuang, China.
Abstract:
AKAP4 as a new Cancer/Testis (CT) antigen is expressed not only in human germ cells, but also expressed in various tumor cells. AKAP4 is correlated with tumor malignancy; however, the role of AKAP4 in esophageal cancer remains unknown. Here we explored the function of AKAP4 in esophageal cancer. We found that AKAP4 mRNA and protein levels were up-regulated in the esophageal cancer tissues compared to normal control. In KYSE150 cell line, inhibition of AKAP4 suppressed cell growth and invasiveness. Overexpression of AKAP4 promoted cell growth and invasiveness. In addition, expression of epithelial markers (E-cadherin and ZO-1) was up-regulated or down-regulated and expression of mesenchymal markers (vimentin and N-cadherin) was down-regulated or up-regulated after knockdown or overexpression of AKAP4 in vitro. In vivo in a xenograft model silencing AKAP4 suppressed tumor growth. We also found that NF-κB p65 bound to AKAP4 promoter and regulated expression of AKAP4. In conclusion, overexpression of AKAP4 is associated with esophageal cancer progression. Inhibition of AKAP4 leads to suppressed growth and invasion of esophageal cancer.
Insights
A-kinase anchor protein 4 (AKAP4) is elevated in esophageal cancer, promoting tumor growth and invasion. Inhibiting AKAP4 suppressed cancer progression in vitro and in vivo, highlighting its role as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- A-kinase anchor protein 4 (AKAP4) is a Cancer/Testis antigen found in germ cells and various tumors.
- AKAP4 expression correlates with tumor malignancy, but its role in esophageal cancer is uncharacterized.
Purpose of the Study:
- To investigate the function and clinical significance of AKAP4 in esophageal cancer.
- To elucidate the regulatory mechanisms of AKAP4 expression in esophageal cancer cells.
Main Methods:
- Quantitative analysis of AKAP4 mRNA and protein levels in esophageal cancer tissues and cell lines.
- In vitro studies involving AKAP4 knockdown and overexpression in KYSE150 cells.
- In vivo xenograft mouse model to assess tumor growth.
- Analysis of epithelial and mesenchymal markers.
- Chromatin immunoprecipitation to study NF-κB p65 binding to the AKAP4 promoter.
Main Results:
- AKAP4 mRNA and protein levels were significantly upregulated in esophageal cancer tissues compared to normal controls.
- AKAP4 inhibition suppressed esophageal cancer cell proliferation and invasion, while overexpression promoted these processes.
- AKAP4 modulation affected the expression of epithelial-mesenchymal transition markers (E-cadherin, ZO-1, vimentin, N-cadherin).
- Silencing AKAP4 suppressed tumor growth in vivo.
- NF-κB p65 was identified as a regulator of AKAP4 expression.
Conclusions:
- Overexpression of AKAP4 is associated with esophageal cancer progression and malignancy.
- AKAP4 plays a crucial role in promoting esophageal cancer cell growth and invasion.
- Targeting AKAP4 represents a potential therapeutic strategy for esophageal cancer.
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