TGF-βRII/EP300/SMAD4 cascade signaling pathway promotes invasion and glycolysis in oral squamous cell carcinoma.

Abstract

INTRODUCTION:

EP300 is considered to be a cancer suppressor gene that plays a role in tumor development, but some studies have reported that it is not an oral squamous cell carcinoma suppressor gene, because there was neither epigenetic inactivation of the gene nor a mutation resulting in functional impairment. However, there is no relevant study on whether EP300 is the exact carcinogenic effect and its mechanisms of carcinogenic effects in oral squamous cell carcinoma.

METHODS:

Western blot analysis and quantitative real time polymerase chain reaction experiments verified the protein and mRNA expression of EP300 in oral squamous cell carcinoma; The effects of EP300 knockout on glucose consumption and lactic acid production were detected by glycolysis experiments; The relationship between pathway-related proteins and EP300 was verified by bioinformatics analysis and co-immunoprecipitation experiment.

RESULTS:

Our experimental results confirm that the protein and mRNA of EP300 are highly expressed in oral squamous cell carcinoma, and after knocking out the EP300, the glycolysis ability, invasion, migration, and other biological functions of oral squamous cell carcinoma, are inhibited at the same time. Pathway-related experiments have confirmed that EP300 plays a role in promoting cancer through the transforming growth factor-beta receptor II (TGF-βRII)/EP300/Smad4 cascade pathway.

CONCLUSION:

EP300 plays a carcinogenic role in OSCC showed that the TGF-βRII/EP300/Smad4 cascade pathway is involved in oral squamous cell carcinoma.

• Authors: Dandan Zhang, Yanshuang Peng, Gaoren Lin, Qian Xiao, Han Liu, Xiaoxu Nan, Jinpeng Han, Runzhe Zhao, Yuzhu Wang, Jialin Liu, Ying Liu
• Journal: Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology (J Oral Pathol Med) Vol. 52 Issue 6 Pg. 483-492 (Jul 2023) ISSN: 1600-0714 [Electronic] Denmark
• PMID: 36916236 (Publication Type: Journal Article)
• Copyright: © 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• E1A-Associated p300 Protein
• EP300 protein, human
• Smad4 Protein
• SMAD4 protein, human
• TGFBR2 protein, human

Topics

• Humans
• Carcinoma, Squamous Cell (pathology)
• Cell Line, Tumor
• Cell Proliferation
• E1A-Associated p300 Protein (genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• Glycolysis
• Head and Neck Neoplasms (genetics)
• Mouth Neoplasms (pathology)
• Signal Transduction
• Smad4 Protein (genetics, metabolism)
• Squamous Cell Carcinoma of Head and Neck (genetics)