TTYH1 and TTYH2 Serve as LRRC8A-Independent Volume-Regulated Anion Channels in Cancer Cells
Volume-regulated anion channels (VRACs) are involved in cellular functions such as regulation of cell volume, proliferation, migration, and cell death. Although leucine-rich repeat−containing 8A (LRRC8A) has been characterized as a molecular component of VRACs, here we show that Drosophila...
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MDPI AG
2019-06-01
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| Online Access: | https://www.mdpi.com/2073-4409/8/6/562 |
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| author | Yeonju Bae Ajung Kim Chang-Hoon Cho Donggyu Kim Hyun-Gug Jung Seong-Seop Kim Jiyun Yoo Jae-Yong Park Eun Mi Hwang |
| author_facet | Yeonju Bae Ajung Kim Chang-Hoon Cho Donggyu Kim Hyun-Gug Jung Seong-Seop Kim Jiyun Yoo Jae-Yong Park Eun Mi Hwang |
| author_sort | Yeonju Bae |
| collection | DOAJ |
| description | Volume-regulated anion channels (VRACs) are involved in cellular functions such as regulation of cell volume, proliferation, migration, and cell death. Although leucine-rich repeat−containing 8A (LRRC8A) has been characterized as a molecular component of VRACs, here we show that Drosophila melanogaster tweety homologue 1 and 2 (TTYH1 and TTYH2) are critical for VRAC currents in cancer cells. LRRC8A-independent VRAC currents were present in the gastric cancer cell line SNU-601, but almost completely absent in its cisplatin-resistant derivative SNU-601-R10 (R10). The VRAC current in R10 was partially restored by treatment with trichostatin A (TSA), a histone deacetylase inhibitor. Based on microarray expression profiling of these cells, we selected two chloride channels, TTYH1 and TTYH2, as VRAC candidates. VRAC currents were completely absent from TTYH1- and TTYH2-deficient SNU-601 cells, and were clearly restored by expression of TTYH1 or TTYH2. In addition, we examined the expression of TTYH1 or TTYH2 in several cancer cell lines and found that VRAC currents of these cells were abolished by gene silencing of TTYH1 or TTYH2. Taken together, our data clearly show that TTYH1 and TTYH2 can act as LRRC8A-independent VRACs, suggesting novel therapeutic approaches for VRACs in cancer cells. |
| first_indexed | 2024-03-12T06:41:39Z |
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| id | doaj.art-ed8e3afeff8b4e7489ee6101d89ecc79 |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-12T06:41:39Z |
| publishDate | 2019-06-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-ed8e3afeff8b4e7489ee6101d89ecc792023-09-03T00:58:11ZengMDPI AGCells2073-44092019-06-018656210.3390/cells8060562cells8060562TTYH1 and TTYH2 Serve as LRRC8A-Independent Volume-Regulated Anion Channels in Cancer CellsYeonju Bae0Ajung Kim1Chang-Hoon Cho2Donggyu Kim3Hyun-Gug Jung4Seong-Seop Kim5Jiyun Yoo6Jae-Yong Park7Eun Mi Hwang8College School of Biosystem and Biomedical Science of Health Science, Korea University, Seoul 02841, KoreaCenter for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, KoreaCollege School of Biosystem and Biomedical Science of Health Science, Korea University, Seoul 02841, KoreaNamhae Garlic Research Institute, Gyeongnam 52430, KoreaCollege School of Biosystem and Biomedical Science of Health Science, Korea University, Seoul 02841, KoreaCollege School of Biosystem and Biomedical Science of Health Science, Korea University, Seoul 02841, KoreaDivision of Applied Life Science (BK21 Plus), Research Institute of Life Sciences, Gyeongsang National University, Jinju 52828, KoreaCollege School of Biosystem and Biomedical Science of Health Science, Korea University, Seoul 02841, KoreaCenter for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, KoreaVolume-regulated anion channels (VRACs) are involved in cellular functions such as regulation of cell volume, proliferation, migration, and cell death. Although leucine-rich repeat−containing 8A (LRRC8A) has been characterized as a molecular component of VRACs, here we show that Drosophila melanogaster tweety homologue 1 and 2 (TTYH1 and TTYH2) are critical for VRAC currents in cancer cells. LRRC8A-independent VRAC currents were present in the gastric cancer cell line SNU-601, but almost completely absent in its cisplatin-resistant derivative SNU-601-R10 (R10). The VRAC current in R10 was partially restored by treatment with trichostatin A (TSA), a histone deacetylase inhibitor. Based on microarray expression profiling of these cells, we selected two chloride channels, TTYH1 and TTYH2, as VRAC candidates. VRAC currents were completely absent from TTYH1- and TTYH2-deficient SNU-601 cells, and were clearly restored by expression of TTYH1 or TTYH2. In addition, we examined the expression of TTYH1 or TTYH2 in several cancer cell lines and found that VRAC currents of these cells were abolished by gene silencing of TTYH1 or TTYH2. Taken together, our data clearly show that TTYH1 and TTYH2 can act as LRRC8A-independent VRACs, suggesting novel therapeutic approaches for VRACs in cancer cells.https://www.mdpi.com/2073-4409/8/6/562VRACTTYH1TTYH2LRRC8Acancer cells |
| spellingShingle | Yeonju Bae Ajung Kim Chang-Hoon Cho Donggyu Kim Hyun-Gug Jung Seong-Seop Kim Jiyun Yoo Jae-Yong Park Eun Mi Hwang TTYH1 and TTYH2 Serve as LRRC8A-Independent Volume-Regulated Anion Channels in Cancer Cells Cells VRAC TTYH1 TTYH2 LRRC8A cancer cells |
| title | TTYH1 and TTYH2 Serve as LRRC8A-Independent Volume-Regulated Anion Channels in Cancer Cells |
| title_full | TTYH1 and TTYH2 Serve as LRRC8A-Independent Volume-Regulated Anion Channels in Cancer Cells |
| title_fullStr | TTYH1 and TTYH2 Serve as LRRC8A-Independent Volume-Regulated Anion Channels in Cancer Cells |
| title_full_unstemmed | TTYH1 and TTYH2 Serve as LRRC8A-Independent Volume-Regulated Anion Channels in Cancer Cells |
| title_short | TTYH1 and TTYH2 Serve as LRRC8A-Independent Volume-Regulated Anion Channels in Cancer Cells |
| title_sort | ttyh1 and ttyh2 serve as lrrc8a independent volume regulated anion channels in cancer cells |
| topic | VRAC TTYH1 TTYH2 LRRC8A cancer cells |
| url | https://www.mdpi.com/2073-4409/8/6/562 |
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