PI3K–AKT–mTOR pathway proteins are differently expressed in oral carcinogenesis

Abstract

Our study demonstrated higher pAKT and pmTOR expression during carcinogenesis of oral mucosa, differing considerably among OED and OSCC specimens when compared to NDOT. These proteins can be considered potential diagnostic markers for early detection of cancer.

Phosphorylated ribosomal protein S6 correlation with p21 expression and inverse association with tumor size in oral squamous cell carcinoma

“…Accordingly, in the context of OSCC, mTOR activation has also been reported in the vast majority of cases. Martins et al found mTOR activation in 77.4% of cases, and herein we detected over 80%. This highlights the relevance of this pathway as a promising therapeutic target for pharmacological intervention in HNSCC .…”

“…Chaisuparat et al reported S6 phosphorylation in 100% of oral epithelial dysplasias, and in 88.67% of OSCC, indicating that S6 phosphorylation is active in early stages of oral tumorigenesis. In line with these findings, Martins et al studied the expression pattern of several components of the PI3K‐AKT‐mTOR pathway in hyperkeratotic oral mucosa, oral epithelial dysplasia, and OSCC, and found that the percentages of cases with phosphorylated S6 were 52.9%, 70.8%, and 77.4%, respectively. In good agreement with these data, our findings show a high prevalence of S6 phosphorylation in OSCC specimens higher than 80%.…”

“…Despite the high prevalence of phosphorylated S6 in cancer, immunoexpression of this protein is found in benign tissues once the ribosomal S6K is associated with several cellular functions, including protein synthesis, mRNA processing, glucose homeostasis, cell growth, and survival. 15 The clinical impact of mTOR activation depends on the tumor type, as it has been revealed in 3 recent metaanalyses. [54][55][56] All of them have been established that mTOR activation is associated with worse prognosis in gynecological, gastrointestinal, and head and neck cancers; however, it is not associated with worse prognosis in breast cancer or even associated with good prognosis in some breast cancer types 57 or in lung cancer, 54 and it is inconclusive in prostate cancers.…”

“…Activation of the PI3K/AKT/mTOR signalling pathway is considered to play a crucial role in human neoplasms, therefore, numerous drugs targeting this pathway have been developed and are currently in clinical trials. Importantly enough, the PI3K/AKT/mTOR signaling pathway has emerged as one of the most frequently deregulated in HNSCC showing numerous alterations of various upstream and downstream components; however, it is fundamental to identify specifically those clinically relevant and to establish their impact on prognosis and patient survival. The serine‐threonine kinase mTOR is a key downstream protein kinase of the PI3K/AKT signalling pathway, where numerous cellular signalling pathways converge and is involved in the pathogenesis of several human cancers .…”

“…However, in this study, we did not find any relationship between the S6 phosphorylation status and p53 immunoexpression. Despite the high prevalence of phosphorylated S6 in cancer, immunoexpression of this protein is found in benign tissues once the ribosomal S6K is associated with several cellular functions, including protein synthesis, mRNA processing, glucose homeostasis, cell growth, and survival …”