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.

VMP1: a multifaceted regulator of cellular homeostasis with implications in disease pathology

“…Autophagy, a conserved cellular pathway, is fundamental to the maintenance of cellular homeostasis through the degradation and recycling of intracellular components ( Klionsky, 2005 ; Mizushima and Komatsu, 2011 ; Lin et al, 2024 ). It plays a critical role in various physiological processes and has been implicated in the pathology of a wide spectrum of diseases, including neurodegenerative disorders ( Liénard et al, 2024 ; Panwar et al, 2024 ) and cancer ( Mathur et al, 2024 ; Rajendran et al, 2024 ; Yang et al, 2024 ). VMP1, a transmembrane protein that orchestrates key steps in the autophagic process, from the nucleation of autophagosomes to their fusion with lysosomes for cargo degradation ( Ropolo et al, 2007 ; Mizushima and Komatsu, 2011 ; Hamasaki et al, 2013 ; Parzych and Klionsky, 2014 ; Wang et al, 2020b ; Wang et al, 2021b ; Dong et al, 2021 ; Jiang et al, 2022 ).…”