Genetic disruption of tubulin acetyltransferase, αTAT1, inhibits proliferation and invasion of colon cancer cells through decreases in Wnt1/β-catenin signaling

Oh, Somi; You, Eunae; Ko, Panseon; Jeong, Jangho; Keum, Seula; Rhee, Sangmyung

doi:10.1016/j.bbrc.2016.11.039

Cited by 32 publications

(26 citation statements)

References 27 publications

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“…HMGN2 is an anti-tumor effector molecule of CD8 + T cells, FOXO3 is a core tumor suppressor in breast cancer; downregulation of PPP2R5E is a common event in acute myeloid leukemia [38,39,40]. However, the ATAT1 activity is required for microtubule organization, it is specifically upregulated in colon cancer tissue and LDHA has an aberrantly high expression in multiple cancers [41,42].…”

Section: Discussionmentioning

confidence: 99%

Circulating miRNA Profiling in Plasma Samples of Ovarian Cancer Patients

Penyige

Márton

Soltész

et al. 2019

IJMS

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Ovarian cancer is one of the most common cancer types in women characterized by a high mortality rate due to lack of early diagnosis. Circulating miRNAs besides being important regulators of cancer development could be potential biomarkers to aid diagnosis. We performed the circulating miRNA expression analysis in plasma samples obtained from ovarian cancer patients stratified into FIGO I, FIGO III, and FIGO IV stages and from healthy females using the NanoString quantitative assay. Forty-five miRNAs were differentially expressed, out of these 17 miRNAs showed significantly different expression between controls and patients, 28 were expressed only in patients, among them 19 were expressed only in FIGO I patients. Differentially expressed miRNAs were ranked by the network-based analysis to assess their importance. Target genes of the differentially expressed miRNAs were identified then functional annotation of the target genes by the GO and KEGG-based enrichment analysis was carried out. A general and an ovary-specific protein–protein interaction network was constructed from target genes. Results of our network and the functional enrichment analysis suggest that besides HSP90AA1, MYC, SP1, BRCA1, RB1, CFTR, STAT3, E2F1, ERBB2, EZH2, and MET genes, additional genes which are enriched in cell cycle regulation, FOXO, TP53, PI-3AKT, AMPK, TGFβ, ERBB signaling pathways and in the regulation of gene expression, proliferation, cellular response to hypoxia, and negative regulation of the apoptotic process, the GO terms have central importance in ovarian cancer development. The aberrantly expressed miRNAs might be considered as potential biomarkers for the diagnosis of ovarian cancer after validation of these results in a larger cohort of ovarian cancer patients.

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Section: Discussionmentioning

confidence: 99%

Circulating miRNA Profiling in Plasma Samples of Ovarian Cancer Patients

Penyige

Márton

Soltész

et al. 2019

IJMS

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“…In lung cancer, ATAT1 plays a key role in cell migration and invasion through the modulation of epithelial-mesenchymal transition and cell polarity [41]. In colon cancer, ATAT1 downregulation inhibits cell proliferation and cell invasion through modulation of Wnt1/β-catenin signaling [42]. Our results indicate that the anti-migratory effects of CPTH6 on lung cancer cells are dependent of its effect on α-tubulin acetylation, thus suggesting that this compound may also inhibit ATAT1, in addition to GNC5 and pCAF.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of lysine acetyltransferases impairs tumor angiogenesis acting on both endothelial and tumor cells

Martile

Gabellini

Desideri

et al. 2020

J Exp Clin Cancer Res

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Background: Understanding the signalling pathways involved in angiogenesis, and developing anti-angiogenic drugs are one of the major focuses on cancer research. Herein, we assessed the effect of CPTH6, a lysine acetyltransferase inhibitor and anti-tumoral compound, on angiogenesis-related properties of both endothelial and cancer cells. Methods: The in vitro effect of CPTH6 on protein acetylation and anti-angiogenic properties on endothelial and lung cancer cells was evaluated via wound healing, trans-well invasion and migration, tube formation, immunoblotting and immunofluorescence. Matrigel plug assay, zebrafish embryo and mouse xenograft models were used to evaluate in vivo anti-angiogenic effect of CPTH6. Results: CPTH6 impaired in vitro endothelial angiogenesis-related functions, and decreased the in vivo vascularization both in mice xenografts and zebrafish embryos. Mechanistically, CPTH6 reduced α-tubulin acetylation and induced accumulation of acetylated microtubules in the perinuclear region of endothelial cells. Interestingly, CPTH6 also affected the angiogenesis-related properties of lung cancer cells, and conditioned media derived from CPTH6-treated lung cancer cells impaired endothelial cells morphogenesis. CPTH6 also modulated the VEGF/VEGFR2 pathway, and reshaped cytoskeletal organization of lung cancer cells. Finally, anti-migratory effect of CPTH6, dependent on α-tubulin acetylation, was also demonstrated by genetic approaches in lung cancer cells. Conclusion: Overall, this study indicates that α-tubulin acetylation could play a role in the anti-angiogenic effect of CPTH6 and, more in general, it adds information to the role of histone acetyltransferases in tumor angiogenesis, and proposes the inhibition of these enzymes as an antiangiogenic therapy of cancer.

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“…αTAT1 KO using the CRISPR-Cas9 system was performed as previously described [ 39 ]. Annealed sgRNA was cloned into the plasmid lentiCRISPR v2.…”

Section: Methodsmentioning

confidence: 99%

Potent Small-Molecule Inhibitors Targeting Acetylated Microtubules as Anticancer Agents Against Triple-Negative Breast Cancer

et al. 2020

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Microtubules are one of the major targets for anticancer drugs because of their role in cell proliferation and migration. However, as anticancer drugs targeting microtubules have side effects, including the death of normal cells, it is necessary to develop anticancer agents that can target microtubules by specifically acting on cancer cells only. In this study, we identified chemicals that can act as anticancer agents by specifically binding to acetylated microtubules, which are predominant in triple-negative breast cancer (TNBC). The chemical compounds disrupted acetylated microtubule lattices by interfering with microtubule access to alpha-tubulin acetyltransferase 1 (αTAT1), a major acetyltransferase of microtubules, resulting in the increased apoptotic cell death of MDA-MB-231 cells (a TNBC cell line) compared with other cells, such as MCF-10A and MCF-7, which lack microtubule acetylation. Moreover, mouse xenograft experiments showed that treatment with the chemical compounds markedly reduced tumor growth progression. Taken together, the newly identified chemical compounds can be selective for acetylated microtubules and act as potential therapeutic agents against microtubule acetylation enrichment in TNBC.

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Genetic disruption of tubulin acetyltransferase, αTAT1, inhibits proliferation and invasion of colon cancer cells through decreases in Wnt1/β-catenin signaling

Cited by 32 publications

References 27 publications

Circulating miRNA Profiling in Plasma Samples of Ovarian Cancer Patients

Circulating miRNA Profiling in Plasma Samples of Ovarian Cancer Patients

Inhibition of lysine acetyltransferases impairs tumor angiogenesis acting on both endothelial and tumor cells

Potent Small-Molecule Inhibitors Targeting Acetylated Microtubules as Anticancer Agents Against Triple-Negative Breast Cancer

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