Microtubule Acetylation Controls MDA-MB-231 Breast Cancer Cell Invasion through the Modulation of Endoplasmic Reticulum Stress
| Autor: | Sangmyung Rhee, Seongeun Song, Jee-Hye Choi, Panseon Ko, Ye Eun Hwang, Jangho Jeong, Jung-Woong Kim, Seula Keum |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Microtubules chemistry.chemical_compound 0302 clinical medicine Tumor Microenvironment Biology (General) Spectroscopy Chemistry Tunicamycin Acetylation General Medicine unfolded protein response Endoplasmic Reticulum Stress Computer Science Applications Gene Expression Regulation Neoplastic 030220 oncology & carcinogenesis Microtubule Proteins Female ER stress QH301-705.5 extracellular matrix Breast Neoplasms Article Catalysis Inorganic Chemistry microtubule acetylation 03 medical and health sciences Breast cancer breast cancer Downregulation and upregulation Acetyltransferases Cell Line Tumor medicine Animals Humans Neoplasm Invasiveness Physical and Theoretical Chemistry Molecular Biology QD1-999 Endoplasmic reticulum Organic Chemistry Cancer medicine.disease 030104 developmental biology Cancer cell Cancer research Unfolded protein response |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 6018, p 6018 (2021) International Journal of Molecular Sciences Volume 22 Issue 11 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | During aggressive cancer progression, cancer cells adapt to unique microenvironments by withstanding various cellular stresses, including endoplasmic reticulum (ER) stress. However, the mechanism whereby cancer cells overcome the ER stress to survive remains to be elucidated. Herein, we demonstrated that microtubule acetylation in cancer cells grown on a stiff matrix promotes cancer progression by preventing excessive ER stress. Downregulation of microtubule acetylation using shRNA or CRSIPR/Cas9 techniques targeting ATAT1, which encodes α-tubulin N-acetyltransferase (αTAT1), resulted in the upregulation of ER stress markers, changes in ER morphology, and enhanced tunicamycin-induced UPR signaling in cancer cells. A set of genes involved in cancer progression, especially focal adhesion genes, were downregulated in both ATAT1-knockout and tunicamycin-treated cells, whereas ATAT1 overexpression restored the gene expression inhibited by tunicamycin. Finally, the expression of ATAT1 and ER stress marker genes were negatively correlated in various breast cancer types. Taken together, our results suggest that disruption of microtubule acetylation is a potent therapeutic tool for preventing breast cancer progression through the upregulation of ER stress. Moreover, ATAT1 and ER stress marker genes may be useful diagnostic markers in various breast cancer types. |
| Databáze: | OpenAIRE |
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