Stimulation of hERG1 channel activity promotes a calciumdependent degradation of cyclin E2, but not cyclin E1, in breast cancer cells
Mathew Perez-Neut, Andrew Shum, Bruce D. Cuevas, Richard Miller, Saverio Gentile*
Cyclin E2 gene amplification, but not cyclin E1, has been recently defined as marker for poor prognosis in breast cancer, and appears to play a major role in proliferation and therapeutic resistance in several breast cancer cells. Our laboratory has previously reported that stimulation of the hERG1 potassium channel with selective activators led to down-regulation of cyclin E2 in breast cancer cells. In this work, we demonstrate that stimulation of hERG1 promotes an ubiquitin-proteasomedependent degradation of cyclin E2 in multiple breast cancer cell lines representing Luminal A, HER2+ and Trastuzumab-resistant breast cancer cells. In addition we have also reveal that hERG1 stimulation induces an increase in intracellular calcium that is required for cyclin E2 degradation. This novel function for hERG1 activity was specific for cyclin E2, as cyclins A, B, D E1 were unaltered by the treatment. Our results reveal a novel mechanism by which hERG1 activation impacts the tumor marker cyclin E2 that is independent of cyclin E1, and suggest a potential therapeutic use for hERG1 channel activators.
https://doi.org/10.18632/oncotarget.2829
Calcium-dependent degradation
Cyclin E2
HERG1
10.18632/oncotarget.2829
Dive into the research topics of 'Stimulation of hERG1 channel activity promotes a calciumdependent degradation of cyclin E2, but not cyclin E1, in breast cancer cells'. Together they form a unique fingerprint.
Cycline Pharmacology, Toxicology and Pharmaceutical Science 100%
Cyclin E2 Biochemistry, Genetics and Molecular Biology 70%
cancer INIS 60%
breasts INIS 60%
Breast Cancer Pharmacology, Toxicology and Pharmaceutical Science 60%
Breast Immunology and Microbiology 50%
Cancer Cell Biochemistry, Genetics and Molecular Biology 40%
stimulation INIS 40%
Perez-Neut, M., Shum, A., Cuevas, B. D., Miller, R., & Gentile, S. (2015). Stimulation of hERG1 channel activity promotes a calciumdependent degradation of cyclin E2, but not cyclin E1, in breast cancer cells. Oncotarget, 6(3), 1631-1639. https://doi.org/10.18632/oncotarget.2829
Perez-Neut, Mathew ; Shum, Andrew ; Cuevas, Bruce D. et al. / Stimulation of hERG1 channel activity promotes a calciumdependent degradation of cyclin E2, but not cyclin E1, in breast cancer cells. In: Oncotarget. 2015 ; Vol. 6, No. 3. pp. 1631-1639.
@article{16b8bb6a2eb0470692e203bd7a3e611e,
title = "Stimulation of hERG1 channel activity promotes a calciumdependent degradation of cyclin E2, but not cyclin E1, in breast cancer cells",
abstract = "Cyclin E2 gene amplification, but not cyclin E1, has been recently defined as marker for poor prognosis in breast cancer, and appears to play a major role in proliferation and therapeutic resistance in several breast cancer cells. Our laboratory has previously reported that stimulation of the hERG1 potassium channel with selective activators led to down-regulation of cyclin E2 in breast cancer cells. In this work, we demonstrate that stimulation of hERG1 promotes an ubiquitin-proteasomedependent degradation of cyclin E2 in multiple breast cancer cell lines representing Luminal A, HER2+ and Trastuzumab-resistant breast cancer cells. In addition we have also reveal that hERG1 stimulation induces an increase in intracellular calcium that is required for cyclin E2 degradation. This novel function for hERG1 activity was specific for cyclin E2, as cyclins A, B, D E1 were unaltered by the treatment. Our results reveal a novel mechanism by which hERG1 activation impacts the tumor marker cyclin E2 that is independent of cyclin E1, and suggest a potential therapeutic use for hERG1 channel activators.",
keywords = "Breast cancer, Calcium-dependent degradation, Cyclin E2, HERG1",
author = "Mathew Perez-Neut and Andrew Shum and Cuevas, {Bruce D.} and Richard Miller and Saverio Gentile",
doi = "10.18632/oncotarget.2829",
journal = "Oncotarget",
publisher = "Impact Journals",
Perez-Neut, M, Shum, A, Cuevas, BD, Miller, R & Gentile, S 2015, 'Stimulation of hERG1 channel activity promotes a calciumdependent degradation of cyclin E2, but not cyclin E1, in breast cancer cells', Oncotarget, vol. 6, no. 3, pp. 1631-1639. https://doi.org/10.18632/oncotarget.2829
Stimulation of hERG1 channel activity promotes a calciumdependent degradation of cyclin E2, but not cyclin E1, in breast cancer cells. / Perez-Neut, Mathew; Shum, Andrew; Cuevas, Bruce D. et al.
In: Oncotarget, Vol. 6, No. 3, 2015, p. 1631-1639.
T1 - Stimulation of hERG1 channel activity promotes a calciumdependent degradation of cyclin E2, but not cyclin E1, in breast cancer cells
AU - Perez-Neut, Mathew
AU - Shum, Andrew
AU - Cuevas, Bruce D.
AU - Miller, Richard
AU - Gentile, Saverio
N2 - Cyclin E2 gene amplification, but not cyclin E1, has been recently defined as marker for poor prognosis in breast cancer, and appears to play a major role in proliferation and therapeutic resistance in several breast cancer cells. Our laboratory has previously reported that stimulation of the hERG1 potassium channel with selective activators led to down-regulation of cyclin E2 in breast cancer cells. In this work, we demonstrate that stimulation of hERG1 promotes an ubiquitin-proteasomedependent degradation of cyclin E2 in multiple breast cancer cell lines representing Luminal A, HER2+ and Trastuzumab-resistant breast cancer cells. In addition we have also reveal that hERG1 stimulation induces an increase in intracellular calcium that is required for cyclin E2 degradation. This novel function for hERG1 activity was specific for cyclin E2, as cyclins A, B, D E1 were unaltered by the treatment. Our results reveal a novel mechanism by which hERG1 activation impacts the tumor marker cyclin E2 that is independent of cyclin E1, and suggest a potential therapeutic use for hERG1 channel activators.
AB - Cyclin E2 gene amplification, but not cyclin E1, has been recently defined as marker for poor prognosis in breast cancer, and appears to play a major role in proliferation and therapeutic resistance in several breast cancer cells. Our laboratory has previously reported that stimulation of the hERG1 potassium channel with selective activators led to down-regulation of cyclin E2 in breast cancer cells. In this work, we demonstrate that stimulation of hERG1 promotes an ubiquitin-proteasomedependent degradation of cyclin E2 in multiple breast cancer cell lines representing Luminal A, HER2+ and Trastuzumab-resistant breast cancer cells. In addition we have also reveal that hERG1 stimulation induces an increase in intracellular calcium that is required for cyclin E2 degradation. This novel function for hERG1 activity was specific for cyclin E2, as cyclins A, B, D E1 were unaltered by the treatment. Our results reveal a novel mechanism by which hERG1 activation impacts the tumor marker cyclin E2 that is independent of cyclin E1, and suggest a potential therapeutic use for hERG1 channel activators.
KW - Calcium-dependent degradation
KW - Cyclin E2
KW - HERG1
U2 - 10.18632/oncotarget.2829
DO - 10.18632/oncotarget.2829
JO - Oncotarget
JF - Oncotarget
Perez-Neut M, Shum A, Cuevas BD, Miller R, Gentile S. Stimulation of hERG1 channel activity promotes a calciumdependent degradation of cyclin E2, but not cyclin E1, in breast cancer cells. Oncotarget. 2015;6(3):1631-1639. doi: 10.18632/oncotarget.2829