TRPM4 channel is involved in regulating epithelial to mesenchymal transition, migration, and invasion of prostate cancer cell lines

Alfredo I. Sagredo, Eduardo A. Sagredo, Victor Pola, César Echeverría, Rodrigo Andaur, Luis Michea, Andrés Stutzin, Felipe Simon, Katherine Marcelain, Ricardo Armisén

Resultado de la investigación: Article

4 Citas (Scopus)

Resumen

Transient Receptor Potential Melastatin 4 (TRPM4) is a Ca2+-activated and voltage-dependent monovalent cation channel, which depolarizes the plasma cell membrane, thereby modulating Ca2+ influx across Ca2+-permeable pathways. TRPM4 is involved in different physiological processes such as T cell activation and the migration of endothelial and certain immune cells. Overexpression of this channel has been reported in various types of tumors including prostate cancer. In this study, a significant overexpression of TRPM4 was found only in samples from cancer with a Gleason score higher than 7, which are more likely to spread. To evaluate whether TRPM4 overexpression was related to the spreading capability of tumors, TRPM4 was knockdown by using shRNAs in PC3 prostate cancer cells and the effect on cellular migration and invasion was analyzed. PC3 cells with reduced levels of TRPM4 (shTRPM4) display a decrease of the migration/invasion capability. A reduction in the expression of Snail1, a canonical epithelial to mesenchymal transition (EMT) transcription factor, was also observed. Consistently, these cells showed a significant change in the expression of key EMT markers such as MMP9, E-cadherin/N-cadherin, and vimentin, indicating a partial reversion of the EMT process. Whereas, the overexpression of TRPM4 in LnCaP cells resulted in increased levels of Snail1, reduction in the expression of E-cadherin and increase in their migration potential. This study suggests a new and indirect mechanism of regulation of migration/invasion process by TRPM4 in prostate cancer cells, by inducing the expression of Snail1 gene and consequently, increasing the EMT.

Idioma originalEnglish
PublicaciónJournal of Cellular Physiology
DOI
EstadoAccepted/In press - 1 ene 2018

Huella dactilar

Epithelial-Mesenchymal Transition
Prostatic Neoplasms
Cells
Cell Line
Cadherins
Cell membranes
Cell Membrane
Physiological Phenomena
Tumors
Monovalent Cations
Neoplasms
Neoplasm Grading
Vimentin
Plasma Cells
Cell Movement
T-cells
Transcription Factors
T-Lymphocytes
Gene Expression
Genes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Citar esto

Sagredo, Alfredo I. ; Sagredo, Eduardo A. ; Pola, Victor ; Echeverría, César ; Andaur, Rodrigo ; Michea, Luis ; Stutzin, Andrés ; Simon, Felipe ; Marcelain, Katherine ; Armisén, Ricardo. / TRPM4 channel is involved in regulating epithelial to mesenchymal transition, migration, and invasion of prostate cancer cell lines. En: Journal of Cellular Physiology. 2018.
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title = "TRPM4 channel is involved in regulating epithelial to mesenchymal transition, migration, and invasion of prostate cancer cell lines",
abstract = "Transient Receptor Potential Melastatin 4 (TRPM4) is a Ca2+-activated and voltage-dependent monovalent cation channel, which depolarizes the plasma cell membrane, thereby modulating Ca2+ influx across Ca2+-permeable pathways. TRPM4 is involved in different physiological processes such as T cell activation and the migration of endothelial and certain immune cells. Overexpression of this channel has been reported in various types of tumors including prostate cancer. In this study, a significant overexpression of TRPM4 was found only in samples from cancer with a Gleason score higher than 7, which are more likely to spread. To evaluate whether TRPM4 overexpression was related to the spreading capability of tumors, TRPM4 was knockdown by using shRNAs in PC3 prostate cancer cells and the effect on cellular migration and invasion was analyzed. PC3 cells with reduced levels of TRPM4 (shTRPM4) display a decrease of the migration/invasion capability. A reduction in the expression of Snail1, a canonical epithelial to mesenchymal transition (EMT) transcription factor, was also observed. Consistently, these cells showed a significant change in the expression of key EMT markers such as MMP9, E-cadherin/N-cadherin, and vimentin, indicating a partial reversion of the EMT process. Whereas, the overexpression of TRPM4 in LnCaP cells resulted in increased levels of Snail1, reduction in the expression of E-cadherin and increase in their migration potential. This study suggests a new and indirect mechanism of regulation of migration/invasion process by TRPM4 in prostate cancer cells, by inducing the expression of Snail1 gene and consequently, increasing the EMT.",
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year = "2018",
month = "1",
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TRPM4 channel is involved in regulating epithelial to mesenchymal transition, migration, and invasion of prostate cancer cell lines. / Sagredo, Alfredo I.; Sagredo, Eduardo A.; Pola, Victor; Echeverría, César; Andaur, Rodrigo; Michea, Luis; Stutzin, Andrés; Simon, Felipe; Marcelain, Katherine; Armisén, Ricardo.

En: Journal of Cellular Physiology, 01.01.2018.

Resultado de la investigación: Article

TY - JOUR

T1 - TRPM4 channel is involved in regulating epithelial to mesenchymal transition, migration, and invasion of prostate cancer cell lines

AU - Sagredo, Alfredo I.

AU - Sagredo, Eduardo A.

AU - Pola, Victor

AU - Echeverría, César

AU - Andaur, Rodrigo

AU - Michea, Luis

AU - Stutzin, Andrés

AU - Simon, Felipe

AU - Marcelain, Katherine

AU - Armisén, Ricardo

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Transient Receptor Potential Melastatin 4 (TRPM4) is a Ca2+-activated and voltage-dependent monovalent cation channel, which depolarizes the plasma cell membrane, thereby modulating Ca2+ influx across Ca2+-permeable pathways. TRPM4 is involved in different physiological processes such as T cell activation and the migration of endothelial and certain immune cells. Overexpression of this channel has been reported in various types of tumors including prostate cancer. In this study, a significant overexpression of TRPM4 was found only in samples from cancer with a Gleason score higher than 7, which are more likely to spread. To evaluate whether TRPM4 overexpression was related to the spreading capability of tumors, TRPM4 was knockdown by using shRNAs in PC3 prostate cancer cells and the effect on cellular migration and invasion was analyzed. PC3 cells with reduced levels of TRPM4 (shTRPM4) display a decrease of the migration/invasion capability. A reduction in the expression of Snail1, a canonical epithelial to mesenchymal transition (EMT) transcription factor, was also observed. Consistently, these cells showed a significant change in the expression of key EMT markers such as MMP9, E-cadherin/N-cadherin, and vimentin, indicating a partial reversion of the EMT process. Whereas, the overexpression of TRPM4 in LnCaP cells resulted in increased levels of Snail1, reduction in the expression of E-cadherin and increase in their migration potential. This study suggests a new and indirect mechanism of regulation of migration/invasion process by TRPM4 in prostate cancer cells, by inducing the expression of Snail1 gene and consequently, increasing the EMT.

AB - Transient Receptor Potential Melastatin 4 (TRPM4) is a Ca2+-activated and voltage-dependent monovalent cation channel, which depolarizes the plasma cell membrane, thereby modulating Ca2+ influx across Ca2+-permeable pathways. TRPM4 is involved in different physiological processes such as T cell activation and the migration of endothelial and certain immune cells. Overexpression of this channel has been reported in various types of tumors including prostate cancer. In this study, a significant overexpression of TRPM4 was found only in samples from cancer with a Gleason score higher than 7, which are more likely to spread. To evaluate whether TRPM4 overexpression was related to the spreading capability of tumors, TRPM4 was knockdown by using shRNAs in PC3 prostate cancer cells and the effect on cellular migration and invasion was analyzed. PC3 cells with reduced levels of TRPM4 (shTRPM4) display a decrease of the migration/invasion capability. A reduction in the expression of Snail1, a canonical epithelial to mesenchymal transition (EMT) transcription factor, was also observed. Consistently, these cells showed a significant change in the expression of key EMT markers such as MMP9, E-cadherin/N-cadherin, and vimentin, indicating a partial reversion of the EMT process. Whereas, the overexpression of TRPM4 in LnCaP cells resulted in increased levels of Snail1, reduction in the expression of E-cadherin and increase in their migration potential. This study suggests a new and indirect mechanism of regulation of migration/invasion process by TRPM4 in prostate cancer cells, by inducing the expression of Snail1 gene and consequently, increasing the EMT.

KW - EMT

KW - invasion

KW - prostate cancer

KW - Snail1

KW - TRPM4

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U2 - 10.1002/jcp.27371

DO - 10.1002/jcp.27371

M3 - Article

AN - SCOPUS:85055274416

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

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