AKT and ERK1/2 inhibition can reduce cancer stem-like cells and epithelial-mesenchymal transition induced by multiple radiation in HNSCC

Introduction:

Irradiation is one of the standard therapies in HNSCC and has been linked to an enhanced tumor migration. We previously reported that this increased tumor migration upon irradiation is dependent on GSK3β inactivation and can be reversed by inhibition of either AKT, ERK1/2 or p38 MAPK signaling. Most experimental studies investigate effects induced by single dose irradiation.

Method and Material:

In this study, we tried to discover the effects promoted by a multiple radiation dose of 2 Gy on 5 consecutive days regarding cell proliferation, migration, invasion and cell signaling. This irradiation regime by us is clinically more realistic and could increase the chance to find possible links to therapy problems like local and distant recurrences which occur around 50% following radiotherapy.

Results:

We detected that multiple irradiated cells in HNSCC express features which are linked to epithelial-mesenchymal-transition (EMT) in Western Blot analysis and in spheroids. Furthermore, they show a significantly increased behavior of invasion and express markers which are linked to cancer stem-like cells. Inhibition of AKT or ERK1/2 signaling reverses EMT and cancer stem like markers under multiple irradiation in HNSCC.

Discussion:

These findings could be of use in the development of new treatments to prevent local or distant recurrences in the future.

Publication History

Publication Date:
18 April 2018 (online)