NRF3 activates mTORC1 arginine-dependently for cancer cell viability
Summary: Cancer cells coordinate the mTORC1 signals and the related metabolic pathways to robustly and rapidly grow in response to nutrient conditions. Although a CNC-family transcription factor NRF3 promotes cancer development, the biological relevance between NRF3 function and mTORC1 signals in ca...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223001220 |
| _version_ | 1797903327640420352 |
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| author | Shuuhei Hirose Tsuyoshi Waku Misato Tani Haruka Masuda Keiko Endo Sanae Ashitani Iori Aketa Hina Kitano Sota Nakada Ayaka Wada Atsushi Hatanaka Tsuyoshi Osawa Tomoyoshi Soga Akira Kobayashi |
| author_facet | Shuuhei Hirose Tsuyoshi Waku Misato Tani Haruka Masuda Keiko Endo Sanae Ashitani Iori Aketa Hina Kitano Sota Nakada Ayaka Wada Atsushi Hatanaka Tsuyoshi Osawa Tomoyoshi Soga Akira Kobayashi |
| author_sort | Shuuhei Hirose |
| collection | DOAJ |
| description | Summary: Cancer cells coordinate the mTORC1 signals and the related metabolic pathways to robustly and rapidly grow in response to nutrient conditions. Although a CNC-family transcription factor NRF3 promotes cancer development, the biological relevance between NRF3 function and mTORC1 signals in cancer cells remains unknown. Hence, we showed that NRF3 contributes to cancer cell viability through mTORC1 activation in response to amino acids, particularly arginine. NRF3 induced SLC38A9 and RagC expression for the arginine-dependent mTORC1 recruitment onto lysosomes, and it also enhanced RAB5-mediated bulk macropinocytosis and SLC7A1-mediated selective transport for arginine loading into lysosomes. Besides, the inhibition of the NRF3–mTORC1 axis impaired mitochondrial function, leading to cancer cell apoptosis. Consistently, the aberrant upregulation of the axis caused tumor growth and poor prognosis. In conclusion, this study sheds light on the unique function of NRF3 in arginine-dependent mTORC1 activation and the pathophysiological aspects of the NRF3–mTORC1 axis in cancer development. |
| first_indexed | 2024-04-10T09:31:08Z |
| format | Article |
| id | doaj.art-94a3d01baf604a83a67455cb7ad7597c |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T09:31:08Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-94a3d01baf604a83a67455cb7ad7597c2023-02-19T04:27:04ZengElsevieriScience2589-00422023-02-01262106045NRF3 activates mTORC1 arginine-dependently for cancer cell viabilityShuuhei Hirose0Tsuyoshi Waku1Misato Tani2Haruka Masuda3Keiko Endo4Sanae Ashitani5Iori Aketa6Hina Kitano7Sota Nakada8Ayaka Wada9Atsushi Hatanaka10Tsuyoshi Osawa11Tomoyoshi Soga12Akira Kobayashi13Laboratory for Genetic Code, Graduate School of Life and Medical Sciences, Doshisha University, 1–3 Miyakodani, Tatara, Kyotanabe, Kyoto 610–0394, Japan; Research Fellow of Japan Society for the Promotion of ScienceLaboratory for Genetic Code, Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto 610–0394, Japan; Corresponding authorLaboratory for Genetic Code, Graduate School of Life and Medical Sciences, Doshisha University, 1–3 Miyakodani, Tatara, Kyotanabe, Kyoto 610–0394, JapanLaboratory for Genetic Code, Graduate School of Life and Medical Sciences, Doshisha University, 1–3 Miyakodani, Tatara, Kyotanabe, Kyoto 610–0394, JapanInstitute for Advanced Biosciences, Keio University, Kakuganji, Tsuruoka 997-0052, JapanInstitute for Advanced Biosciences, Keio University, Kakuganji, Tsuruoka 997-0052, JapanLaboratory for Genetic Code, Graduate School of Life and Medical Sciences, Doshisha University, 1–3 Miyakodani, Tatara, Kyotanabe, Kyoto 610–0394, JapanLaboratory for Genetic Code, Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto 610–0394, JapanLaboratory for Genetic Code, Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto 610–0394, JapanLaboratory for Genetic Code, Graduate School of Life and Medical Sciences, Doshisha University, 1–3 Miyakodani, Tatara, Kyotanabe, Kyoto 610–0394, JapanLaboratory for Genetic Code, Graduate School of Life and Medical Sciences, Doshisha University, 1–3 Miyakodani, Tatara, Kyotanabe, Kyoto 610–0394, JapanDivision of Integrative Nutriomics and Oncology, RCAST, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, JapanInstitute for Advanced Biosciences, Keio University, Kakuganji, Tsuruoka 997-0052, JapanLaboratory for Genetic Code, Graduate School of Life and Medical Sciences, Doshisha University, 1–3 Miyakodani, Tatara, Kyotanabe, Kyoto 610–0394, Japan; Laboratory for Genetic Code, Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto 610–0394, Japan; Corresponding authorSummary: Cancer cells coordinate the mTORC1 signals and the related metabolic pathways to robustly and rapidly grow in response to nutrient conditions. Although a CNC-family transcription factor NRF3 promotes cancer development, the biological relevance between NRF3 function and mTORC1 signals in cancer cells remains unknown. Hence, we showed that NRF3 contributes to cancer cell viability through mTORC1 activation in response to amino acids, particularly arginine. NRF3 induced SLC38A9 and RagC expression for the arginine-dependent mTORC1 recruitment onto lysosomes, and it also enhanced RAB5-mediated bulk macropinocytosis and SLC7A1-mediated selective transport for arginine loading into lysosomes. Besides, the inhibition of the NRF3–mTORC1 axis impaired mitochondrial function, leading to cancer cell apoptosis. Consistently, the aberrant upregulation of the axis caused tumor growth and poor prognosis. In conclusion, this study sheds light on the unique function of NRF3 in arginine-dependent mTORC1 activation and the pathophysiological aspects of the NRF3–mTORC1 axis in cancer development.http://www.sciencedirect.com/science/article/pii/S2589004223001220Cellular physiologyCell biologyCancer |
| spellingShingle | Shuuhei Hirose Tsuyoshi Waku Misato Tani Haruka Masuda Keiko Endo Sanae Ashitani Iori Aketa Hina Kitano Sota Nakada Ayaka Wada Atsushi Hatanaka Tsuyoshi Osawa Tomoyoshi Soga Akira Kobayashi NRF3 activates mTORC1 arginine-dependently for cancer cell viability iScience Cellular physiology Cell biology Cancer |
| title | NRF3 activates mTORC1 arginine-dependently for cancer cell viability |
| title_full | NRF3 activates mTORC1 arginine-dependently for cancer cell viability |
| title_fullStr | NRF3 activates mTORC1 arginine-dependently for cancer cell viability |
| title_full_unstemmed | NRF3 activates mTORC1 arginine-dependently for cancer cell viability |
| title_short | NRF3 activates mTORC1 arginine-dependently for cancer cell viability |
| title_sort | nrf3 activates mtorc1 arginine dependently for cancer cell viability |
| topic | Cellular physiology Cell biology Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223001220 |
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