The effect of genetic variants of SLC22A18 on proliferation, migration, and invasion of colon cancer cells
Abstract Solute carrier family (SLC) transporters are expressed in the digestive system and play important roles in maintaining physiological functions in the body. In addition, SLC transporters act as oncoproteins or tumor-suppressor proteins during the development, progression, and metastasis of v...
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| Format: | Article |
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Nature Portfolio
2024-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-54658-w |
| _version_ | 1827327705366921216 |
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| author | Hyo Sook Song Seung Yeon Ha Jin-Young Kim Minsuk Kim Ji Ha Choi |
| author_facet | Hyo Sook Song Seung Yeon Ha Jin-Young Kim Minsuk Kim Ji Ha Choi |
| author_sort | Hyo Sook Song |
| collection | DOAJ |
| description | Abstract Solute carrier family (SLC) transporters are expressed in the digestive system and play important roles in maintaining physiological functions in the body. In addition, SLC transporters act as oncoproteins or tumor-suppressor proteins during the development, progression, and metastasis of various digestive system cancers. SLC22A18, a member of the SLC22 gene family, is an orphan transporter with an unknown endogenous substrate. Previous study revealed that SLC22A18 is downregulated in colorectal cancer tissues and that it acts as a suppressor in colorectal cancer, although the effects of SLC22A18 variants on colon cancer cell proliferation, migration, and invasion are unknown. Therefore, in this study, we identified SLC22A18 variants found in multiple populations by searching public databases and determined the in vitro effects of these missense variations on transporter expression and cancer progression. Our results indicated that three missense SLC22A18 variants—p.Ala6Thr, p.Arg12Gln, and p.Arg86His—had significantly lower cell expression than the wild type, possibly owing to intracellular degradation. Furthermore, these three variants caused significantly higher proliferation, migration, and invasion of colon cancer cells than the wild type. Our findings suggest that missense variants of SLC22A18 can potentially serve as biomarkers or prognostic tools that enable clinicians to predict colorectal cancer progression. |
| first_indexed | 2024-03-07T15:06:07Z |
| format | Article |
| id | doaj.art-53aee8e4dc754114b78e9041f5e1d900 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:06:07Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-53aee8e4dc754114b78e9041f5e1d9002024-03-05T18:54:10ZengNature PortfolioScientific Reports2045-23222024-02-0114111010.1038/s41598-024-54658-wThe effect of genetic variants of SLC22A18 on proliferation, migration, and invasion of colon cancer cellsHyo Sook Song0Seung Yeon Ha1Jin-Young Kim2Minsuk Kim3Ji Ha Choi4Department of Pharmacology, Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans UniversityDepartment of Pharmacology, Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans UniversityDepartment of Pharmacology, Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans UniversityDepartment of Pharmacology, Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans UniversityDepartment of Pharmacology, Inflammation-Cancer Microenvironment Research Center, College of Medicine, Ewha Womans UniversityAbstract Solute carrier family (SLC) transporters are expressed in the digestive system and play important roles in maintaining physiological functions in the body. In addition, SLC transporters act as oncoproteins or tumor-suppressor proteins during the development, progression, and metastasis of various digestive system cancers. SLC22A18, a member of the SLC22 gene family, is an orphan transporter with an unknown endogenous substrate. Previous study revealed that SLC22A18 is downregulated in colorectal cancer tissues and that it acts as a suppressor in colorectal cancer, although the effects of SLC22A18 variants on colon cancer cell proliferation, migration, and invasion are unknown. Therefore, in this study, we identified SLC22A18 variants found in multiple populations by searching public databases and determined the in vitro effects of these missense variations on transporter expression and cancer progression. Our results indicated that three missense SLC22A18 variants—p.Ala6Thr, p.Arg12Gln, and p.Arg86His—had significantly lower cell expression than the wild type, possibly owing to intracellular degradation. Furthermore, these three variants caused significantly higher proliferation, migration, and invasion of colon cancer cells than the wild type. Our findings suggest that missense variants of SLC22A18 can potentially serve as biomarkers or prognostic tools that enable clinicians to predict colorectal cancer progression.https://doi.org/10.1038/s41598-024-54658-w |
| spellingShingle | Hyo Sook Song Seung Yeon Ha Jin-Young Kim Minsuk Kim Ji Ha Choi The effect of genetic variants of SLC22A18 on proliferation, migration, and invasion of colon cancer cells Scientific Reports |
| title | The effect of genetic variants of SLC22A18 on proliferation, migration, and invasion of colon cancer cells |
| title_full | The effect of genetic variants of SLC22A18 on proliferation, migration, and invasion of colon cancer cells |
| title_fullStr | The effect of genetic variants of SLC22A18 on proliferation, migration, and invasion of colon cancer cells |
| title_full_unstemmed | The effect of genetic variants of SLC22A18 on proliferation, migration, and invasion of colon cancer cells |
| title_short | The effect of genetic variants of SLC22A18 on proliferation, migration, and invasion of colon cancer cells |
| title_sort | effect of genetic variants of slc22a18 on proliferation migration and invasion of colon cancer cells |
| url | https://doi.org/10.1038/s41598-024-54658-w |
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