The protein kinase Akt induces epithelial mesenchymal transition and promotes enhanced motility and invasiveness of squamous cell carcinoma lines.

TLDR

Epithelial‑mesenchymal transition, driven in part by AKT activation, enables carcinoma cells to acquire fibroblast‑like traits, reduce adhesion, and gain motility that facilitates invasion and metastasis. Constitutively active Akt in squamous cell carcinoma lines triggers EMT—down‑regulating desmoplakin, E‑cadherin, and β‑catenin, up‑regulating vimentin—leading to loss of epithelial morphology, diminished cell‑cell adhesion, enhanced motility on fibronectin, and increased invasiveness in vivo, suggesting AKT inhibition could curb tumor spread.

Abstract

Epithelial-mesenchymal transition (EMT) is an important process during development and oncogenesis by which epithelial cells acquire fibroblast-like properties and show reduced intercellular adhesion and increased motility. Squamous cell carcinoma lines engineered to express constitutively active Akt underwent EMT, characterized by down-regulation of the epithelial markers desmoplakin, E-cadherin, and beta-catenin and up-regulation of the mesenchymal marker vimentin. The cells lost epithelial cell morphology and acquired fibroblast-like properties. Additionally, E-cadherin was down-regulated transcriptionally. The cells expressing constitutively active Akt exhibited reduced cell-cell adhesion, increased motility on fibronectin-coated surfaces, and increased invasiveness in animals. AKT is activated in many human carcinomas, and the AKT-driven EMT may confer the motility required for tissue invasion and metastasis. These findings suggest that future therapies based on AKT inhibition may complement conventional treatments by controlling tumor cell invasion and metastasis.