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.

About a Possible Impact of Endodontic Infections by Fusobacterium nucleatum or Porphyromonas gingivalis on Oral Carcinogenesis: A Literature Overview

“…Consistently, other studies have described the positive impact of each of the aforecited molecules on OSCC cell growth [56,132,133]. In addition, the same cytokines could favor OSCC progression also because of their capability of stimulating the invasiveness of carci-noma cells and of maintaining or even exacerbating their dedifferentiation status [132][133][134][135][136] (Figure 1). Moreover, due to their immunosuppressive properties, VEGF, FGF-2, and TGF-β1 could support OSCC growth also in an indirect fashion, that is, by inhibiting the immune response that OSCC-infiltrating leukocytes exert against the cancer cells [137-139] (Figure 1).…”

“…Specifically, here we report that P. gingivalis and/or F. nucleatum spark, in dental pulp cells or periodontal cells, the synthesis of cytokines that, in turn, trigger the survival, growth, and invasion of OSCC cells [115][116][117][124][125][126][127][132][133][134][135][136]. Furthermore, the two bacteria and the cytokines induced by them stop the differentiation of DPSCs and periodontal stem cells while concomitantly stimulating their growth and invasiveness [118][119][120][121][174][175][176][177] and releasing mutagenic substances [28][29][30][31].…”