αTAT1-induced tubulin acetylation promotes ameloblastoma migration and invasion

Shohei Yoshimoto,Hiromitsu Morita,Kazuhiko Okamura,Akimitsu Hiraki,Shuichi Hashimoto

doi:10.1038/s41374-021-00671-w

Shohei Yoshimoto, Hiromitsu Morita + Show 3 more

Open Access

https://doi.org/10.1038/s41374-021-00671-w

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Abstract

AbstractAmeloblastoma (AB) is the most common benign epithelial odontogenic tumor occurring in the jawbone. AB is a slowly growing tumor but sometimes shows a locally invasive and an aggressive growth pattern with a marked bone resorption. In addition, the local recurrence and distant metastasis of AB also sometimes occurs, which resembles one of the typical malignant potentials. From these points of view, to understand better the mechanisms of AB cell migration or invasion is necessary for the better clinical therapy and improvements of the patients' quality of life. Microtubules in eukaryotic cells reveal the shape of hollow cylinders made up of polymerized alpha (α)- and beta (β)-tubulin dimers and form the cytoskeleton together with microfilaments and intermediate filaments. Microtubules play important roles in cell migration by undergoing assembly and disassembly with post-translational modifications. Stability of microtubules caused by their acetylation is involved in cell migration. In this study, we investigated the expression and distribution of acetylated α-tubulin and alpha-tubulin N-acetyltransferase 1 (αTAT1), an enzyme which acetylates Lys-40 in α-tubulin, in AB specimens, and analyzed how tubulin was acetylated by αTAT1 activation in a human AB cell line, AM-1. Finally, we clarified that TGF-β-activated kinase1 (TAK1) was phosphorylated by TGF-β stimulation, then, induced tubulin acetylation via αTAT1 activation, which subsequently activated the migration and invasion of AB cells.

Highlights

Ameloblastoma (AB) is the most common benign epithelial odontogenic tumor occurring in the mandibular or maxillary bones[1].The growth pattern of AB is usually slow, but sometimes shows an aggressive appearance with a locally invasive growth and bone resorption[2]
Co-expression of acetylated α-tubulin and α-tubulin and alpha-tubulin N-acetyltransferase 1 (αTAT1) in the cytoplasm of tumor cells was apparent especially at the tip of the invasive front (Fig. 1B). These findings suggested that tubulin acetylation was closely related to the αTAT1 expression and played a key role in the AB cell invasion and tumor progression
The histopathological and immunohistochemical analyses for AB tissues and in vitro studies using AM-1 cells revealed that transforming growth factor-β (TGF-β) stimulation activated TGF-β-activated kinase1 (TAK1) by inducing its phosphorylation, Fig. 3 Functional analyses of tubulin acetylation on the cell migration and invasion in AM-1 cells by the inhibition of αTAT1

Summary

Introduction

Ameloblastoma (AB) is the most common benign epithelial odontogenic tumor occurring in the mandibular or maxillary bones[1].The growth pattern of AB is usually slow, but sometimes shows an aggressive appearance with a locally invasive growth and bone resorption[2]. The local recurrence or distant metastasis of this tumor sometimes occurs, which resembles one of the typical malignant potentials. From these points of view, to understand better the mechanisms of AB cell invasion or migration could contribute to the development of the better therapeutic strategy and potential biomarkers for the diagnosis and to the improvement of the patients’ quality of life. It is well known that cytoskeletons, such as actin filaments and microtubules, play important roles. Microtubules play important roles in cell migration by undergoing assembly and disassembly with post-translational modifications. Alpha-tubulin N-acetyltransferase 1 (αTAT1), an enzyme which acetylates Lys-40 in α tubulin, contributes microtubules stability[5]. In the head and neck tumors progression, roles of tubulin acetylation remain unclear

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