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Tytuł:
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Telomerase inhibition regulates EMT mechanism in breast cancer stem cells.
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Autorzy:
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Kusoglu A; Ege University Medical School, Department of Medical Biology, Turkey. Electronic address: .
Goker Bagca B; Ege University Medical School, Department of Medical Biology, Turkey.
Ozates Ay NP; Ege University Medical School, Department of Medical Biology, Turkey.
Gunduz C; Ege University Medical School, Department of Medical Biology, Turkey.
Biray Avci C; Ege University Medical School, Department of Medical Biology, Turkey.
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Źródło:
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Gene [Gene] 2020 Oct 30; Vol. 759, pp. 145001. Date of Electronic Publication: 2020 Jul 29.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Original Publication: Amsterdam, Elsevier/North-Holland, 1976-
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MeSH Terms:
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Epithelial-Mesenchymal Transition*
Aminobenzoates/*pharmacology
Breast Neoplasms/*metabolism
Enzyme Inhibitors/*pharmacology
Naphthalenes/*pharmacology
Neoplastic Stem Cells/*drug effects
Cell Movement ; Cell Proliferation ; Female ; Humans ; MCF-7 Cells ; Neoplastic Stem Cells/physiology ; Telomerase/antagonists & inhibitors
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Contributed Indexing:
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Keywords: BIBR1532; Breast cancer stem cells; Cancer stem cells; Epithelial mesenchymal transition; Metastasis; Migration; Sphere formation; Telomerase
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Substance Nomenclature:
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0 (Aminobenzoates)
0 (BIBR 1532)
0 (Enzyme Inhibitors)
0 (Naphthalenes)
EC 2.7.7.49 (Telomerase)
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Entry Date(s):
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Date Created: 20200802 Date Completed: 20200909 Latest Revision: 20220416
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Update Code:
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20240104
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DOI:
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10.1016/j.gene.2020.145001
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PMID:
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32738420
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Backround: CSCs having the common features of high telomerase activity and high migration and invasion capabilities play a vital role as the initiators of metastasis. Small molecule BIBR1532 has been shown to target cancer cells by inhibiting telomerase. Recent studies have suggested that telomerase activity is associated with epithelial mesenchymal transition (EMT). EMT program, which causes epithelial cells to acquire a mesenchymal morphology, is known to play a significant role in cancer metastasis.
Methods: The hypothesis of our study was that suppression of telomerase in breast cancer and cancer stem cells would interrupt EMT mechanism. Cytotoxicity of BIBR1532 was evaluated using WST-1 assay in all cell lines and the effects of BIBR1532 on apoptosis were investigated with Annexin V. Migration rate of the cells was examined by wound healing assay and sphere forming capacities were observed by hanging drop test. Finally, the expression of 84 EMT-related genes was analyzed by real-time qPCR.
Results: The IC 50 values for the MDA-MB-231 and breast epithelial stem cells of BIBR1532 were analyzed as 18.04 and 38.71 µl at 72 h, respectively. Interestingly, apoptosis was only induced in stem cells. In hanging drop test, sphere areas were reduced in stem cells treated with BIBR1532. In wound healing assay, BIBR1532 decreased the migration rate of stem cells. Together with this, expression of EMT-related genes were regulated in stem cells towards a epithelial phenotype.
Conclusion: Our obtained results indicated that telomerase inhibition affects the EMT mechanism. The targeted elimination of breast cancer stem cells by a telomerase inhibitor in cancer treatment may limit the mobility and stemness of cancer cells interrupting the EMT mechanism, thus may prevent metastasis.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
