TRPM2 ion channel promotes gastric cancer migration, invasion and tumor growth through the AKT signaling pathway
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 bioe...
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| Veröffentlicht in: | Scientific reports 2019-03, Vol.9 (1), p.4182, Article 4182 |
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| description | 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. |
| doi_str_mv | 10.1038/s41598-019-40330-1 |
| format | Article |
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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. 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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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30862883</pmid><doi>10.1038/s41598-019-40330-1</doi><orcidid>https://orcid.org/0000-0002-1251-5066</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 42/41 631/45/269/1146 631/67/1504/1829 64/60 82/80 96/95 AKT protein Animals Bioenergetics Calcium - metabolism Carcinogenesis - metabolism Carcinogenesis - pathology Cell Line, Tumor Cell Movement Cell Proliferation Cytosol - metabolism Deregulation Down-Regulation Enzyme Activation Epithelial-Mesenchymal Transition Gastric cancer Gene Silencing Health risks HEK293 Cells Humanities and Social Sciences Humans Male Metastases Metastasis Mice, Inbred NOD Mice, SCID multidisciplinary Neoplasm Invasiveness Proto-Oncogene Proteins c-akt - metabolism PTEN protein Science Science (multidisciplinary) Signal Transduction Stomach Neoplasms - metabolism Stomach Neoplasms - pathology Therapeutic applications Transient receptor potential proteins TRPM Cation Channels - metabolism |
| title | TRPM2 ion channel promotes gastric cancer migration, invasion and tumor growth through the AKT signaling pathway |
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