PI3K/AKT Signaling Pathway Mediated Autophagy in Oral Carcinoma - A Comprehensive Review

Abstract

Oral cancer is the most heterogeneous cancer at clinical and histological levels. PI3K/AKT/mTOR pathway was identified as one of the most commonly modulated signals in oral cancer, which regulates major cellular and metabolic activity of the cell. Thus, various proteins of PI3K/AKT/mTOR pathway were used as therapeutic targets for oral cancer, to design more specific drugs with less off-target toxicity. This review sheds light on the regulation of PI3K/AKT/mTOR, and its role in controlling autophagy and associated apoptosis during the progression and metastasis of oral squamous type of malignancy (OSCC). In addition, we reviewed in detail the upstream activators and the downstream effectors of PI3K/AKT/mTOR signaling as potential therapeutic targets for oral cancer treatment.

Keywords: PI3K/AKT; autophagy; metastasis; oral cancer.

Figure 1

Various Inhibitors that are used as therapeutic agent to target various proteins in PI3/AKT pathway in order to activate autophagy. PI3K: Phosphoinositide-3-kinase; BCR: B-cell antigen receptors; PTEN: Phosphatase and TENsin homolog; PDK1: 3-Phosphoinositide-dependent kinase 1; Akt: Akt serine/threonine kinase family; ULK1: Unc-51 Like Autophagy Activating Kinase 1; ATG: Autophagy Related Gene. (Indicates inhibition…….; Indicates Stimulation →). Created with Biorender in September 2023.

Figure 2

Targets on PI3K/Akt that inhibit the function of various proteins in the pathway to decelerate cell proliferation, angiogenesis, epithelial-mesenchymal transition and promote autophagy-apoptosis axis. Created with Biorender in September 2023.