Organic Anion Transporters (OAT) and Other SLC22 Transporters in Progression of Renal Cell Carcinoma
(1) Background: Many transporters of the SLC22 family (e.g., OAT1, OAT3, OCT2, URAT1, and OCTN2) are highly expressed in the kidney. They transport drugs, metabolites, signaling molecules, antioxidants, nutrients, and gut microbiome products. According to the Remote Sensing and Signaling Theory, SLC...
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| Format: | Article |
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MDPI AG
2022-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/19/4772 |
| _version_ | 1797480204168331264 |
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| author | Thomas C. Whisenant Sanjay K. Nigam |
| author_facet | Thomas C. Whisenant Sanjay K. Nigam |
| author_sort | Thomas C. Whisenant |
| collection | DOAJ |
| description | (1) Background: Many transporters of the SLC22 family (e.g., OAT1, OAT3, OCT2, URAT1, and OCTN2) are highly expressed in the kidney. They transport drugs, metabolites, signaling molecules, antioxidants, nutrients, and gut microbiome products. According to the Remote Sensing and Signaling Theory, SLC22 transporters play a critical role in small molecule communication between organelles, cells and organs as well as between the body and the gut microbiome. This raises the question about the potential role of SLC22 transporters in cancer biology and treatment. (2) Results: In two renal cell carcinoma RNA-seq datasets found in TCGA, KIRC and KIRP, there were multiple differentially expressed (DE) SLC22 transporter genes compared to normal kidney. These included SLC22A6, SLC22A7, SLC22A8, SLC22A12, and SLC22A13. The patients with disease had an association between overall survival and expression for most of these DE genes. In KIRC, the stratification of patient data by pathological tumor characteristics revealed the importance of SLC22A2, SLC22A6, and SLC22A12 in disease progression. Interaction networks combining the SLC22 with ADME genes supported the centrality of SLC22 transporters and other transporters (ABCG2, SLC47A1) in disease progression. (3) Implications: The fact that many of these genes are uric acid transporters is interesting because altered uric acid levels have been associated with kidney cancer. Moreover, these genes play key roles in processing metabolites and chemotherapeutic compounds, thus making them potential therapeutic targets. Finally, our analyses raise the possibility that current approaches may undertreat certain kidney cancer patients with low SLC22 expression and only localized disease while possibly overtreating more advanced disease in patients with higher SLC22 expression. Clinical studies are needed to investigate these possibilities. |
| first_indexed | 2024-03-09T21:56:43Z |
| format | Article |
| id | doaj.art-661a533816e14dba918a74f750cb74ff |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T21:56:43Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-661a533816e14dba918a74f750cb74ff2023-11-23T19:56:21ZengMDPI AGCancers2072-66942022-09-011419477210.3390/cancers14194772Organic Anion Transporters (OAT) and Other SLC22 Transporters in Progression of Renal Cell CarcinomaThomas C. Whisenant0Sanjay K. Nigam1Center for Computational Biology and Bioinformatics, University of California, San Diego, CA 92093-0693, USADepartment of Pediatrics, University of California, San Diego, CA 92093-0693, USA(1) Background: Many transporters of the SLC22 family (e.g., OAT1, OAT3, OCT2, URAT1, and OCTN2) are highly expressed in the kidney. They transport drugs, metabolites, signaling molecules, antioxidants, nutrients, and gut microbiome products. According to the Remote Sensing and Signaling Theory, SLC22 transporters play a critical role in small molecule communication between organelles, cells and organs as well as between the body and the gut microbiome. This raises the question about the potential role of SLC22 transporters in cancer biology and treatment. (2) Results: In two renal cell carcinoma RNA-seq datasets found in TCGA, KIRC and KIRP, there were multiple differentially expressed (DE) SLC22 transporter genes compared to normal kidney. These included SLC22A6, SLC22A7, SLC22A8, SLC22A12, and SLC22A13. The patients with disease had an association between overall survival and expression for most of these DE genes. In KIRC, the stratification of patient data by pathological tumor characteristics revealed the importance of SLC22A2, SLC22A6, and SLC22A12 in disease progression. Interaction networks combining the SLC22 with ADME genes supported the centrality of SLC22 transporters and other transporters (ABCG2, SLC47A1) in disease progression. (3) Implications: The fact that many of these genes are uric acid transporters is interesting because altered uric acid levels have been associated with kidney cancer. Moreover, these genes play key roles in processing metabolites and chemotherapeutic compounds, thus making them potential therapeutic targets. Finally, our analyses raise the possibility that current approaches may undertreat certain kidney cancer patients with low SLC22 expression and only localized disease while possibly overtreating more advanced disease in patients with higher SLC22 expression. Clinical studies are needed to investigate these possibilities.https://www.mdpi.com/2072-6694/14/19/4772kidney cancerremote sensing and signalingSLC22KIRCKIRPSLC22A1 |
| spellingShingle | Thomas C. Whisenant Sanjay K. Nigam Organic Anion Transporters (OAT) and Other SLC22 Transporters in Progression of Renal Cell Carcinoma Cancers kidney cancer remote sensing and signaling SLC22 KIRC KIRP SLC22A1 |
| title | Organic Anion Transporters (OAT) and Other SLC22 Transporters in Progression of Renal Cell Carcinoma |
| title_full | Organic Anion Transporters (OAT) and Other SLC22 Transporters in Progression of Renal Cell Carcinoma |
| title_fullStr | Organic Anion Transporters (OAT) and Other SLC22 Transporters in Progression of Renal Cell Carcinoma |
| title_full_unstemmed | Organic Anion Transporters (OAT) and Other SLC22 Transporters in Progression of Renal Cell Carcinoma |
| title_short | Organic Anion Transporters (OAT) and Other SLC22 Transporters in Progression of Renal Cell Carcinoma |
| title_sort | organic anion transporters oat and other slc22 transporters in progression of renal cell carcinoma |
| topic | kidney cancer remote sensing and signaling SLC22 KIRC KIRP SLC22A1 |
| url | https://www.mdpi.com/2072-6694/14/19/4772 |
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