Protective Role of IRBIT on Sodium Bicarbonate Cotransporter-n1 for Migratory Cancer Cells
IP<sub>3</sub> receptor-binding protein released with IP<sub>3</sub> (IRBIT) interacts with various ion channels and transporters. An electroneutral type of sodium bicarbonate cotransporter, NBCn1, participates in cell migration, and its enhanced expression is related to canc...
| Published in: | Pharmaceutics |
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| Main Authors: | , , |
| Format: | Article |
| Language: | English |
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MDPI AG
2020-08-01
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| Online Access: | https://www.mdpi.com/1999-4923/12/9/816 |
| _version_ | 1849877700757422080 |
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| author | Soyoung Hwang Dong Min Shin Jeong Hee Hong |
| author_facet | Soyoung Hwang Dong Min Shin Jeong Hee Hong |
| author_sort | Soyoung Hwang |
| collection | DOAJ |
| container_title | Pharmaceutics |
| description | IP<sub>3</sub> receptor-binding protein released with IP<sub>3</sub> (IRBIT) interacts with various ion channels and transporters. An electroneutral type of sodium bicarbonate cotransporter, NBCn1, participates in cell migration, and its enhanced expression is related to cancer metastasis. The effect of IRBIT on NBCn1 and its relation to cancer cell migration remain obscure. We therefore aimed to determine the effect of IRBIT on NBCn1 and the regulation of cancer cell migration due to IRBIT-induced alterations in NBCn1 activity. Overexpression of IRBIT enhanced cancer cell migration and NBC activity. Knockdown of IRBIT or NBCn1 and treatment with an NBC-specific inhibitor, S0859, attenuated cell migration. Stimulation with oncogenic epidermal growth factor enhanced the expression of NBCn1 and migration of cancer cells by recruiting IRBIT. The recruited IRBIT stably maintained the expression of the NBCn1 transporter machinery in the plasma membrane. Combined inhibition of IRBIT and NBCn1 dramatically inhibited the migration of cancer cells. Combined modulation of IRBIT and NBCn1 offers an effective strategy for attenuating cancer metastasis. |
| format | Article |
| id | doaj-art-800d9cdf4e494b3f9924e6190feb45cf |
| institution | Directory of Open Access Journals |
| issn | 1999-4923 |
| language | English |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| spelling | doaj-art-800d9cdf4e494b3f9924e6190feb45cf2025-08-20T01:11:04ZengMDPI AGPharmaceutics1999-49232020-08-0112981610.3390/pharmaceutics12090816Protective Role of IRBIT on Sodium Bicarbonate Cotransporter-n1 for Migratory Cancer CellsSoyoung Hwang0Dong Min Shin1Jeong Hee Hong2Department of Physiology, College of Medicine, Department of Health Sciences and Technology, GAIHST, Gachon University, 155 Getbeolro, Yeonsu-gu, Incheon 21999, KoreaDepartment of Oral Biology, Yonsei University College of Dentistry, Seoul 03722, KoreaDepartment of Physiology, College of Medicine, Department of Health Sciences and Technology, GAIHST, Gachon University, 155 Getbeolro, Yeonsu-gu, Incheon 21999, KoreaIP<sub>3</sub> receptor-binding protein released with IP<sub>3</sub> (IRBIT) interacts with various ion channels and transporters. An electroneutral type of sodium bicarbonate cotransporter, NBCn1, participates in cell migration, and its enhanced expression is related to cancer metastasis. The effect of IRBIT on NBCn1 and its relation to cancer cell migration remain obscure. We therefore aimed to determine the effect of IRBIT on NBCn1 and the regulation of cancer cell migration due to IRBIT-induced alterations in NBCn1 activity. Overexpression of IRBIT enhanced cancer cell migration and NBC activity. Knockdown of IRBIT or NBCn1 and treatment with an NBC-specific inhibitor, S0859, attenuated cell migration. Stimulation with oncogenic epidermal growth factor enhanced the expression of NBCn1 and migration of cancer cells by recruiting IRBIT. The recruited IRBIT stably maintained the expression of the NBCn1 transporter machinery in the plasma membrane. Combined inhibition of IRBIT and NBCn1 dramatically inhibited the migration of cancer cells. Combined modulation of IRBIT and NBCn1 offers an effective strategy for attenuating cancer metastasis.https://www.mdpi.com/1999-4923/12/9/816IRBITmigrationsodium bicarbonate cotransportercancer metastasis |
| spellingShingle | Soyoung Hwang Dong Min Shin Jeong Hee Hong Protective Role of IRBIT on Sodium Bicarbonate Cotransporter-n1 for Migratory Cancer Cells IRBIT migration sodium bicarbonate cotransporter cancer metastasis |
| title | Protective Role of IRBIT on Sodium Bicarbonate Cotransporter-n1 for Migratory Cancer Cells |
| title_full | Protective Role of IRBIT on Sodium Bicarbonate Cotransporter-n1 for Migratory Cancer Cells |
| title_fullStr | Protective Role of IRBIT on Sodium Bicarbonate Cotransporter-n1 for Migratory Cancer Cells |
| title_full_unstemmed | Protective Role of IRBIT on Sodium Bicarbonate Cotransporter-n1 for Migratory Cancer Cells |
| title_short | Protective Role of IRBIT on Sodium Bicarbonate Cotransporter-n1 for Migratory Cancer Cells |
| title_sort | protective role of irbit on sodium bicarbonate cotransporter n1 for migratory cancer cells |
| topic | IRBIT migration sodium bicarbonate cotransporter cancer metastasis |
| url | https://www.mdpi.com/1999-4923/12/9/816 |
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