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Establishment of a Clinic-based Biorepository
Published on: May 29, 2017
E47 upregulates ΔNp63α to promote growth of squamous cell carcinoma
Jing Xu1, Fengtian Li1, Ya Gao1
1Center of Growth, Metabolism and Aging, Key Laboratory of Bio-Resource and Eco-Environment, Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, China.
Abstract:
Targeted therapy has greatly improved both survival and prognosis of cancer patients. However, while therapeutic treatment of adenocarcinoma has been advanced greatly, progress in treatment of squamous cell carcinoma (SCC) has been slow and ineffective. Therefore, it is of great importance to decipher mechanisms and identify new drug targets involved in squamous cell carcinoma development. In this study, we demonstrate that E47 plays the distinctive and opposite roles on cell proliferation in adenocarcinoma and squamous cell carcinoma. While E47 suppresses cell proliferation in adenocarcinoma cells, it functions as a oncoprotein to promote cell proliferation and tumor growth of squamous cell carcinoma. Mechanistically, we show that E47 can directly bind to the promoter and transactivate ΔNp63 gene expression in squamous cell carcinoma cells, resulting in upregulation of cyclins D1/E1 and downregulation of p21, and thereby promoting cell proliferation and tumor growth. We further show that expression of E2A (E12/E47) is positively correlated with p63 and that high expression of E2A is associated with poor outcomes in clinical samples of squamous cell carcinoma. These results highlight that the E47-ΔNp63α axis may be potential therapeutic targets for treatment of squamous cell carcinoma.
Insights
E47 protein promotes squamous cell carcinoma growth by activating ΔNp63 gene expression. This contrasts with its role in adenocarcinoma, highlighting E47 as a potential therapeutic target for SCC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Targeted therapies have improved cancer treatment, but progress in squamous cell carcinoma (SCC) lags behind adenocarcinoma.
- Identifying novel therapeutic targets for SCC is crucial due to slow treatment advancements.
Purpose of the Study:
- To investigate the distinct roles of E47 in adenocarcinoma and SCC proliferation.
- To elucidate the molecular mechanisms underlying E47's function in SCC.
- To identify potential therapeutic targets for SCC.
Main Methods:
- Comparative analysis of E47 function in adenocarcinoma and SCC cell lines.
- Investigation of E47's direct binding and transactivation of the ΔNp63 gene promoter.
- Correlation analysis of E2A (E12/E47) expression with p63 and clinical outcomes in SCC patient samples.
Main Results:
- E47 suppresses proliferation in adenocarcinoma but promotes it in SCC, acting as an oncoprotein in SCC.
- E47 directly binds to and transactivates ΔNp63 gene expression in SCC cells.
- Upregulation of cyclins D1/E1 and downregulation of p21 mediated by E47-ΔNp63α axis promotes SCC proliferation and tumor growth.
- High E2A expression correlates positively with p63 and is associated with poor prognosis in SCC patients.
Conclusions:
- The E47-ΔNp63α axis plays a critical role in promoting SCC development and tumor growth.
- This axis represents a promising therapeutic target for the treatment of squamous cell carcinoma.
