Alpha-tubulin acetyltransferase/MEC-17 regulates cancer cell migration and invasion through epithelial–mesenchymal transition suppression and cell polarity disruption

Cheng Che Lee, Yun Ching Cheng, Chi Yen Chang, Chi Min Lin, Jang Yang Chang

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Abstract

MEC-17, a newly identified alpha-tubulin-N-acetyltransferase 1, serves as the major α-tubulin acetyltransferase to promote α-tubulin acetylation in vitro and in vivo. Alteration of α-tubulin acetylation may be involved in morphology regulation, cell migration, and tumour metastasis. However, MEC-17’s role in cell physiology and its effect on epithelial–mesenchymal transition (EMT) and cell polarity remain elusive. In the present study, we characterized the overexpressed or downregulated cell models through gene targeting as MEC-17 gain- or loss-of-function. Overexpression of MEC-17 enhanced the cell spreading area, suppressed pseudopods formation in a three-dimensional (3D) culture system, and inhibited cancer cell migratory and invasive ability and tumour metastasis by orthotopic lung cancer animal model. Furthermore, morphological change and migration inhibition of cancer cells were accompanied by EMT repression, Golgi reorientation, and polarity disruption caused by alteration of cdc42 activity via a decrease in Rho-GAP, ARHGAP21. By contrast, a reduction in endogenous MEC-17 accelerated the pseudopods formation and EMT, and facilitated cell migration and invasion. These results demonstrated the crucial role of MEC-17 in the modulation of intrinsic cell morphogenesis, migration, and invasive function through regulation of EMT and cell polarity.

Original languageEnglish
Article number17477
JournalScientific reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

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Cell Polarity
Cell Movement
Tubulin
Pseudopodia
Acetylation
Neoplasms
Cell Migration Inhibition
Neoplasm Metastasis
Cell Physiological Phenomena
Acetyltransferases
Gene Targeting
Morphogenesis
Lung Neoplasms
Down-Regulation
Animal Models
alpha-tubulin acetylase

All Science Journal Classification (ASJC) codes

  • General

Cite this

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title = "Alpha-tubulin acetyltransferase/MEC-17 regulates cancer cell migration and invasion through epithelial–mesenchymal transition suppression and cell polarity disruption",
abstract = "MEC-17, a newly identified alpha-tubulin-N-acetyltransferase 1, serves as the major α-tubulin acetyltransferase to promote α-tubulin acetylation in vitro and in vivo. Alteration of α-tubulin acetylation may be involved in morphology regulation, cell migration, and tumour metastasis. However, MEC-17’s role in cell physiology and its effect on epithelial–mesenchymal transition (EMT) and cell polarity remain elusive. In the present study, we characterized the overexpressed or downregulated cell models through gene targeting as MEC-17 gain- or loss-of-function. Overexpression of MEC-17 enhanced the cell spreading area, suppressed pseudopods formation in a three-dimensional (3D) culture system, and inhibited cancer cell migratory and invasive ability and tumour metastasis by orthotopic lung cancer animal model. Furthermore, morphological change and migration inhibition of cancer cells were accompanied by EMT repression, Golgi reorientation, and polarity disruption caused by alteration of cdc42 activity via a decrease in Rho-GAP, ARHGAP21. By contrast, a reduction in endogenous MEC-17 accelerated the pseudopods formation and EMT, and facilitated cell migration and invasion. These results demonstrated the crucial role of MEC-17 in the modulation of intrinsic cell morphogenesis, migration, and invasive function through regulation of EMT and cell polarity.",
author = "Lee, {Cheng Che} and Cheng, {Yun Ching} and Chang, {Chi Yen} and Lin, {Chi Min} and Chang, {Jang Yang}",
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T1 - Alpha-tubulin acetyltransferase/MEC-17 regulates cancer cell migration and invasion through epithelial–mesenchymal transition suppression and cell polarity disruption

AU - Lee, Cheng Che

AU - Cheng, Yun Ching

AU - Chang, Chi Yen

AU - Lin, Chi Min

AU - Chang, Jang Yang

PY - 2018/12/1

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