TRPM2 ion channel promotes gastric cancer migration, invasion and tumor growth through the AKT signaling pathway

Shekoufeh Almasi; Andra M. Sterea; Wasundara Fernando; Derek R. Clements; Paola Marcato; David W. Hoskin; Shashi Gujar; Yassine El Hiani

doi:10.1038/s41598-019-40330-1

TRPM2 ion channel promotes gastric cancer migration, invasion and tumor growth through the AKT signaling pathway

Shekoufeh Almasi, Andra M. Sterea, Wasundara Fernando, Derek R. Clements, Paola Marcato, David W. Hoskin, Shashi Gujar, Yassine El Hiani

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

56 Citas (Scopus)

Resumen

Transient Receptor Potential Melastatin-2 (TRPM2) ion channel is emerging as a great therapeutic target in many types of cancer, including gastric cancer – a major health threat of cancer related-death worldwide. Our previous study demonstrated the critical role of TRPM2 in gastric cancer cells bioenergetics and survival; however, its role in gastric cancer metastasis, the major cause of patient death, remains unknown. Here, using molecular and functional assays, we demonstrate that TRPM2 downregulation significantly inhibits the migration and invasion abilities of gastric cancer cells, with a significant reversion in the expression level of metastatic markers. These effects were concomitant with decreased Akt and increased PTEN activities. Finally, TRPM2 silencing resulted in deregulation of metastatic markers and abolished the tumor growth ability of AGS gastric cancer cells in NOD/SCID mice. Taken together, our results provide compelling evidence on the important function of TRPM2 in the modulation of gastric cancer cell invasion likely through controlling the PTEN/Akt pathway.

Idioma original	English
Número de artículo	4182
Publicación	Scientific Reports
Volumen	9
N.º	1
DOI	https://doi.org/10.1038/s41598-019-40330-1
Estado	Published - dic. 1 2019

Nota bibliográfica

Funding Information:
This work was supported by Dalhousie Medical Research Foundation Capital Equipment Grant Competition Research project and the Department of Physiology and Biophysics StartUp funds to Y.E.H.

Publisher Copyright:
© 2019, The Author(s).

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abstract = "Transient Receptor Potential Melastatin-2 (TRPM2) ion channel is emerging as a great therapeutic target in many types of cancer, including gastric cancer – a major health threat of cancer related-death worldwide. Our previous study demonstrated the critical role of TRPM2 in gastric cancer cells bioenergetics and survival; however, its role in gastric cancer metastasis, the major cause of patient death, remains unknown. Here, using molecular and functional assays, we demonstrate that TRPM2 downregulation significantly inhibits the migration and invasion abilities of gastric cancer cells, with a significant reversion in the expression level of metastatic markers. These effects were concomitant with decreased Akt and increased PTEN activities. Finally, TRPM2 silencing resulted in deregulation of metastatic markers and abolished the tumor growth ability of AGS gastric cancer cells in NOD/SCID mice. Taken together, our results provide compelling evidence on the important function of TRPM2 in the modulation of gastric cancer cell invasion likely through controlling the PTEN/Akt pathway.",

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AU - Clements, Derek R.

AU - Marcato, Paola

AU - Hoskin, David W.

AU - Gujar, Shashi

AU - El Hiani, Yassine

N1 - Funding Information: This work was supported by Dalhousie Medical Research Foundation Capital Equipment Grant Competition Research project and the Department of Physiology and Biophysics StartUp funds to Y.E.H. Publisher Copyright: © 2019, The Author(s).

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N2 - Transient Receptor Potential Melastatin-2 (TRPM2) ion channel is emerging as a great therapeutic target in many types of cancer, including gastric cancer – a major health threat of cancer related-death worldwide. Our previous study demonstrated the critical role of TRPM2 in gastric cancer cells bioenergetics and survival; however, its role in gastric cancer metastasis, the major cause of patient death, remains unknown. Here, using molecular and functional assays, we demonstrate that TRPM2 downregulation significantly inhibits the migration and invasion abilities of gastric cancer cells, with a significant reversion in the expression level of metastatic markers. These effects were concomitant with decreased Akt and increased PTEN activities. Finally, TRPM2 silencing resulted in deregulation of metastatic markers and abolished the tumor growth ability of AGS gastric cancer cells in NOD/SCID mice. Taken together, our results provide compelling evidence on the important function of TRPM2 in the modulation of gastric cancer cell invasion likely through controlling the PTEN/Akt pathway.

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TRPM2 ion channel promotes gastric cancer migration, invasion and tumor growth through the AKT signaling pathway

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