Papalazarou, Vasileios and Newman, Alice C. and Huerta-Uribe, Alejandro and Legrave, Nathalie M. and Falcone, Mattia and Zhang, Tong and McGarry, Lynn and Athineos, Dimitris and Shanks, Emma and Blyth, Karen and Vousden, Karen H. and Maddocks, Oliver D. K. (2023) Phenotypic profiling of solute carriers characterises serine transport in cancer. Nature Metabolism, 5. pp. 2148-2168. ISSN 2522-5812
AI Summary:
Serine is a vital amino acid in tumorigenesis. The study identifies SLC6A14, SLC25A15, and SLC12A4 as major cytoplasmic and mitochondrial serine transporters.AI Topics:
Serine is a vital amino acid in tumorigenesis. While cells can perform de novo serine synthesis, most transformed cells rely on serine uptake to meet their increased biosynthetic requirements. Solute carriers (SLCs), a family of transmembrane nutrient transport proteins, are the gatekeepers of amino acid acquisition and exchange in mammalian cells and are emerging as anticancer therapeutic targets; however, the SLCs that mediate serine transport in cancer cells remain unknown. Here we perform an arrayed RNAi screen of SLC-encoding genes while monitoring amino acid consumption and cell proliferation in colorectal cancer cells using metabolomics and high-throughput imaging. We identify SLC6A14 and SLC25A15 as major cytoplasmic and mitochondrial serine transporters, respectively. We also observe that SLC12A4 facilitates serine uptake. Dual targeting of SLC6A14 and either SLC25A15 or SLC12A4 diminishes serine uptake and growth of colorectal cancer cells in vitro and in vivo, particularly in cells with compromised de novo serine biosynthesis. Our results provide insight into the mechanisms that contribute to serine uptake and intracellular handling.
Papalazarou, Vasileios
Author
Papalazarou, Vasileios and Newman, Alice C. and Huerta-Uribe, Alejandro and Legrave, Nathalie M. and Falcone, Mattia and Zhang, Tong and McGarry, Lynn and Athineos, Dimitris and Shanks, Emma and Blyth, Karen and Vousden, Karen H. and Maddocks, Oliver D. K. (2023) Phenotypic profiling of solute carriers characterises serine transport in cancer. Nature Metabolism, 5. pp. 2148-2168. ISSN 2522-5812
See full publications listNewman, Alice C.
Author
Papalazarou, Vasileios and Newman, Alice C. and Huerta-Uribe, Alejandro and Legrave, Nathalie M. and Falcone, Mattia and Zhang, Tong and McGarry, Lynn and Athineos, Dimitris and Shanks, Emma and Blyth, Karen and Vousden, Karen H. and Maddocks, Oliver D. K. (2023) Phenotypic profiling of solute carriers characterises serine transport in cancer. Nature Metabolism, 5. pp. 2148-2168. ISSN 2522-5812
See full publications listHuerta-Uribe, Alejandro
Author
Papalazarou, Vasileios and Newman, Alice C. and Huerta-Uribe, Alejandro and Legrave, Nathalie M. and Falcone, Mattia and Zhang, Tong and McGarry, Lynn and Athineos, Dimitris and Shanks, Emma and Blyth, Karen and Vousden, Karen H. and Maddocks, Oliver D. K. (2023) Phenotypic profiling of solute carriers characterises serine transport in cancer. Nature Metabolism, 5. pp. 2148-2168. ISSN 2522-5812
Papalazarou, Vasileios and Newman, Alice C. and Huerta-Uribe, Alejandro and Legrave, Nathalie M. and Falcone, Mattia and Zhang, Tong and McGarry, Lynn and Athineos, Dimitris and Shanks, Emma and Blyth, Karen and Vousden, Karen H. and Maddocks, Oliver D. K. (2023) Phenotypic profiling of solute carriers characterizes serine transport in cancer. Nature Metabolism, 5 (12). pp. 2148-2168. ISSN 2522-5812
See full publications listLegrave, Nathalie M.
Author
Papalazarou, Vasileios and Newman, Alice C. and Huerta-Uribe, Alejandro and Legrave, Nathalie M. and Falcone, Mattia and Zhang, Tong and McGarry, Lynn and Athineos, Dimitris and Shanks, Emma and Blyth, Karen and Vousden, Karen H. and Maddocks, Oliver D. K. (2023) Phenotypic profiling of solute carriers characterises serine transport in cancer. Nature Metabolism, 5. pp. 2148-2168. ISSN 2522-5812
Papalazarou, Vasileios and Newman, Alice C. and Huerta-Uribe, Alejandro and Legrave, Nathalie M. and Falcone, Mattia and Zhang, Tong and McGarry, Lynn and Athineos, Dimitris and Shanks, Emma and Blyth, Karen and Vousden, Karen H. and Maddocks, Oliver D. K. (2023) Phenotypic profiling of solute carriers characterizes serine transport in cancer. Nature Metabolism, 5 (12). pp. 2148-2168. ISSN 2522-5812
See full publications listFalcone, Mattia
Author
Papalazarou, Vasileios and Newman, Alice C. and Huerta-Uribe, Alejandro and Legrave, Nathalie M. and Falcone, Mattia and Zhang, Tong and McGarry, Lynn and Athineos, Dimitris and Shanks, Emma and Blyth, Karen and Vousden, Karen H. and Maddocks, Oliver D. K. (2023) Phenotypic profiling of solute carriers characterises serine transport in cancer. Nature Metabolism, 5. pp. 2148-2168. ISSN 2522-5812
Papalazarou, Vasileios and Newman, Alice C. and Huerta-Uribe, Alejandro and Legrave, Nathalie M. and Falcone, Mattia and Zhang, Tong and McGarry, Lynn and Athineos, Dimitris and Shanks, Emma and Blyth, Karen and Vousden, Karen H. and Maddocks, Oliver D. K. (2023) Phenotypic profiling of solute carriers characterizes serine transport in cancer. Nature Metabolism, 5 (12). pp. 2148-2168. ISSN 2522-5812
See full publications listZhang, Tong
Author
Papalazarou, Vasileios and Newman, Alice C. and Huerta-Uribe, Alejandro and Legrave, Nathalie M. and Falcone, Mattia and Zhang, Tong and McGarry, Lynn and Athineos, Dimitris and Shanks, Emma and Blyth, Karen and Vousden, Karen H. and Maddocks, Oliver D. K. (2023) Phenotypic profiling of solute carriers characterises serine transport in cancer. Nature Metabolism, 5. pp. 2148-2168. ISSN 2522-5812
See full publications listMcGarry, Lynn
Author
Papalazarou, Vasileios and Newman, Alice C. and Huerta-Uribe, Alejandro and Legrave, Nathalie M. and Falcone, Mattia and Zhang, Tong and McGarry, Lynn and Athineos, Dimitris and Shanks, Emma and Blyth, Karen and Vousden, Karen H. and Maddocks, Oliver D. K. (2023) Phenotypic profiling of solute carriers characterises serine transport in cancer. Nature Metabolism, 5. pp. 2148-2168. ISSN 2522-5812
Papalazarou, Vasileios and Newman, Alice C. and Huerta-Uribe, Alejandro and Legrave, Nathalie M. and Falcone, Mattia and Zhang, Tong and McGarry, Lynn and Athineos, Dimitris and Shanks, Emma and Blyth, Karen and Vousden, Karen H. and Maddocks, Oliver D. K. (2023) Phenotypic profiling of solute carriers characterizes serine transport in cancer. Nature Metabolism, 5 (12). pp. 2148-2168. ISSN 2522-5812
See full publications listAthineos, Dimitris
Author
Papalazarou, Vasileios and Newman, Alice C. and Huerta-Uribe, Alejandro and Legrave, Nathalie M. and Falcone, Mattia and Zhang, Tong and McGarry, Lynn and Athineos, Dimitris and Shanks, Emma and Blyth, Karen and Vousden, Karen H. and Maddocks, Oliver D. K. (2023) Phenotypic profiling of solute carriers characterises serine transport in cancer. Nature Metabolism, 5. pp. 2148-2168. ISSN 2522-5812
See full publications listShanks, Emma
Author
Khalaf, Ahmed and de Beauchamp, Lucie and Kalkman, Eric and Rattigan, Kevin and Himonas, Ekaterini and Jones, Joe and James, Daniel and Shokry, Engy Shokry Abd and Scott, Mary T. and Dunn, Karen and Tardito, Saverio and Copland, Mhairi and Sumpton, David and Shanks, Emma and Helgason, Vignir (2024) Nutrient-sensitizing drug repurposing screen identifies lomerizine as a mitochondrial metabolism inhibitor of chronic myeloid leukemia. Science Translational Medicine, 16 (751): eadi5336. ISSN 1946-6234
Papalazarou, Vasileios and Newman, Alice C. and Huerta-Uribe, Alejandro and Legrave, Nathalie M. and Falcone, Mattia and Zhang, Tong and McGarry, Lynn and Athineos, Dimitris and Shanks, Emma and Blyth, Karen and Vousden, Karen H. and Maddocks, Oliver D. K. (2023) Phenotypic profiling of solute carriers characterises serine transport in cancer. Nature Metabolism, 5. pp. 2148-2168. ISSN 2522-5812
Papalazarou, Vasileios and Newman, Alice C. and Huerta-Uribe, Alejandro and Legrave, Nathalie M. and Falcone, Mattia and Zhang, Tong and McGarry, Lynn and Athineos, Dimitris and Shanks, Emma and Blyth, Karen and Vousden, Karen H. and Maddocks, Oliver D. K. (2023) Phenotypic profiling of solute carriers characterizes serine transport in cancer. Nature Metabolism, 5 (12). pp. 2148-2168. ISSN 2522-5812
See full publications listBlyth, Karen
Author
Elbassioni, Ali Ali Mohamed and Raheem, Anmar A. and Song, Jian and Johnston, Alexander S. and Trivett, Cara and Lin, Hong and Zhang, Haobo and Bradley, Ashley and Higgins, Erin and Mooney, Leanne and Koay, Yen Chin and O'Toole, Dylan and Herzyk, Pawel and Nixon, Colin and Blyth, Karen and O'Sullivan, John F. and Lang, Ninian N. and Berry, Colin and Braun, Thomas and Schiattarella, Gabriele G. and Giacca, Mauro and McBride, Martin W. and Nicklin, Stuart A. and Cameron, Ewan R. and Loughrey, Christopher M. and MacDonald, Eilidh A. (2025) Targeting Runx1 protects against heart failure with preserved ejection fraction. bioRxiv.
Strathearn, Lauren S. and Spender, Lindsay C. and Schoenherr, Christina and Mason, Susan and Edwards, Ruaridh and Blyth, Karen and Inman, Gareth (2024) C1orf106 (INAVA) is a SMAD3-dependent TGF-β target gene that promotes clonogenicity and correlates with poor prognosis in breast cancer. Cells, 13 (18): 1530. ISSN 2073-4409
Mardilovich, Katerina and Naylor, Gregory and Julian, Linda and Phinichkusolchit, Narisa and Keeshan, Karen and Blyth, Karen and Olson, Michael F. (2024) Caspase-resistant ROCK1 expression prolongs survival of Eµ-Myc B cell lymphoma mice. Disease Models and Mechanisms, 17 (5): dmm050631. ISSN 1754-8403
See full publications listVousden, Karen H.
Author
Papalazarou, Vasileios and Newman, Alice C. and Huerta-Uribe, Alejandro and Legrave, Nathalie M. and Falcone, Mattia and Zhang, Tong and McGarry, Lynn and Athineos, Dimitris and Shanks, Emma and Blyth, Karen and Vousden, Karen H. and Maddocks, Oliver D. K. (2023) Phenotypic profiling of solute carriers characterises serine transport in cancer. Nature Metabolism, 5. pp. 2148-2168. ISSN 2522-5812
See full publications listMaddocks, Oliver D. K.
Author
Papalazarou, Vasileios and Newman, Alice C. and Huerta-Uribe, Alejandro and Legrave, Nathalie M. and Falcone, Mattia and Zhang, Tong and McGarry, Lynn and Athineos, Dimitris and Shanks, Emma and Blyth, Karen and Vousden, Karen H. and Maddocks, Oliver D. K. (2023) Phenotypic profiling of solute carriers characterises serine transport in cancer. Nature Metabolism, 5. pp. 2148-2168. ISSN 2522-5812
Papalazarou, Vasileios and Newman, Alice C. and Huerta-Uribe, Alejandro and Legrave, Nathalie M. and Falcone, Mattia and Zhang, Tong and McGarry, Lynn and Athineos, Dimitris and Shanks, Emma and Blyth, Karen and Vousden, Karen H. and Maddocks, Oliver D. K. (2023) Phenotypic profiling of solute carriers characterizes serine transport in cancer. Nature Metabolism, 5 (12). pp. 2148-2168. ISSN 2522-5812
See full publications listAvailable under License Creative Commons Attribution.
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