Interplay of Carbonic Anhydrase IX With Amino Acid and Acid/Base Transporters in the Hypoxic Tumor Microenvironment
Solid tumors are challenged with a hypoxic and nutrient-deprived microenvironment. Hence, hypoxic tumor cells coordinatively increase the expression of nutrient transporters and pH regulators to adapt and meet their bioenergetic and biosynthetic demands. Carbonic Anhydrase IX (CAIX) is a membrane-bo...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2020.602668/full |
| _version_ | 1818157847939121152 |
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| author | Geetha Venkateswaran Geetha Venkateswaran Shoukat Dedhar Shoukat Dedhar Shoukat Dedhar |
| author_facet | Geetha Venkateswaran Geetha Venkateswaran Shoukat Dedhar Shoukat Dedhar Shoukat Dedhar |
| author_sort | Geetha Venkateswaran |
| collection | DOAJ |
| description | Solid tumors are challenged with a hypoxic and nutrient-deprived microenvironment. Hence, hypoxic tumor cells coordinatively increase the expression of nutrient transporters and pH regulators to adapt and meet their bioenergetic and biosynthetic demands. Carbonic Anhydrase IX (CAIX) is a membrane-bound enzyme that plays a vital role in pH regulation in the tumor microenvironment (TME). Numerous studies have established the importance of CAIX in mediating tumor progression and metastasis. To understand the mechanism of CAIX in mediating tumor progression, we performed an unbiased proteomic screen to identify the potential interactors of CAIX in the TME using the proximity-dependent biotin identification (BioID) technique. In this review, we focus on the interactors from this BioID screen that are crucial for nutrient and metabolite transport in the TME. We discuss the role of transport metabolon comprising CAIX and bicarbonate transporters in regulating intra- and extracellular pH of the tumor. We also discuss the role of amino acid transporters that are high confidence interactors of CAIX, in optimizing favorable metabolic state for tumor progression, and give our perspective on the coordinative interplay of CAIX with the amino acid transporters in the hypoxic TME. |
| first_indexed | 2024-12-11T15:20:42Z |
| format | Article |
| id | doaj.art-4678fe0b10314a17af7d32888f2d02a4 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-11T15:20:42Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-4678fe0b10314a17af7d32888f2d02a42022-12-22T01:00:22ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-11-01810.3389/fcell.2020.602668602668Interplay of Carbonic Anhydrase IX With Amino Acid and Acid/Base Transporters in the Hypoxic Tumor MicroenvironmentGeetha Venkateswaran0Geetha Venkateswaran1Shoukat Dedhar2Shoukat Dedhar3Shoukat Dedhar4Department of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC, CanadaInterdisciplinary Oncology Program, The University of British Columbia, Vancouver, BC, CanadaDepartment of Integrative Oncology, British Columbia Cancer Research Centre, Vancouver, BC, CanadaInterdisciplinary Oncology Program, The University of British Columbia, Vancouver, BC, CanadaDepartment of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, CanadaSolid tumors are challenged with a hypoxic and nutrient-deprived microenvironment. Hence, hypoxic tumor cells coordinatively increase the expression of nutrient transporters and pH regulators to adapt and meet their bioenergetic and biosynthetic demands. Carbonic Anhydrase IX (CAIX) is a membrane-bound enzyme that plays a vital role in pH regulation in the tumor microenvironment (TME). Numerous studies have established the importance of CAIX in mediating tumor progression and metastasis. To understand the mechanism of CAIX in mediating tumor progression, we performed an unbiased proteomic screen to identify the potential interactors of CAIX in the TME using the proximity-dependent biotin identification (BioID) technique. In this review, we focus on the interactors from this BioID screen that are crucial for nutrient and metabolite transport in the TME. We discuss the role of transport metabolon comprising CAIX and bicarbonate transporters in regulating intra- and extracellular pH of the tumor. We also discuss the role of amino acid transporters that are high confidence interactors of CAIX, in optimizing favorable metabolic state for tumor progression, and give our perspective on the coordinative interplay of CAIX with the amino acid transporters in the hypoxic TME.https://www.frontiersin.org/articles/10.3389/fcell.2020.602668/fulltumor microenvironmenthypoxiacarbonic anhydrase IXamino acid transporttumor metabolism |
| spellingShingle | Geetha Venkateswaran Geetha Venkateswaran Shoukat Dedhar Shoukat Dedhar Shoukat Dedhar Interplay of Carbonic Anhydrase IX With Amino Acid and Acid/Base Transporters in the Hypoxic Tumor Microenvironment Frontiers in Cell and Developmental Biology tumor microenvironment hypoxia carbonic anhydrase IX amino acid transport tumor metabolism |
| title | Interplay of Carbonic Anhydrase IX With Amino Acid and Acid/Base Transporters in the Hypoxic Tumor Microenvironment |
| title_full | Interplay of Carbonic Anhydrase IX With Amino Acid and Acid/Base Transporters in the Hypoxic Tumor Microenvironment |
| title_fullStr | Interplay of Carbonic Anhydrase IX With Amino Acid and Acid/Base Transporters in the Hypoxic Tumor Microenvironment |
| title_full_unstemmed | Interplay of Carbonic Anhydrase IX With Amino Acid and Acid/Base Transporters in the Hypoxic Tumor Microenvironment |
| title_short | Interplay of Carbonic Anhydrase IX With Amino Acid and Acid/Base Transporters in the Hypoxic Tumor Microenvironment |
| title_sort | interplay of carbonic anhydrase ix with amino acid and acid base transporters in the hypoxic tumor microenvironment |
| topic | tumor microenvironment hypoxia carbonic anhydrase IX amino acid transport tumor metabolism |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2020.602668/full |
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