Targeting Methionine Metabolism Reveals AMPK-SAMTOR Signaling as a Therapeutic Vulnerability in Prostate Cancer
Prostate cancer (PCa) is not only one of the most diagnosed malignancies in men but also a leading cause of cancer-related mortality globally. PCa exhibits unique metabolic dependencies, particularly on lipids and glutamine, unlike many solid tumors, rather than glycolysis. Methionine metabolism pla...
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MDPI AG
2025-05-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/14/5/507 |
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| author | Serdar Arisan Ayyuce Sever Pinar Obakan-Yerlikaya Elif Damla Arisan Pinar Uysal-Onganer |
| author_facet | Serdar Arisan Ayyuce Sever Pinar Obakan-Yerlikaya Elif Damla Arisan Pinar Uysal-Onganer |
| author_sort | Serdar Arisan |
| collection | DOAJ |
| description | Prostate cancer (PCa) is not only one of the most diagnosed malignancies in men but also a leading cause of cancer-related mortality globally. PCa exhibits unique metabolic dependencies, particularly on lipids and glutamine, unlike many solid tumors, rather than glycolysis. Methionine metabolism plays a crucial role in these metabolic pathways, contributing to polyamine biosynthesis, DNA methylation, and cellular signaling processes. Here, we demonstrate that methionine deprivation induces selective vulnerability in AMPK-deficient PC3 PCa cells by disrupting SAMTOR–mTOR signaling and triggering oxidative stress, lipid depletion, and autophagic responses. Through functional and proteomic analyses, we show that SAMTOR directly interacts with p-AMPK and modulates cell fate under methionine-limited conditions. Our findings establish a mechanistic link between methionine sensing and metabolic stress signaling in PCa, offering a new avenue for targeted intervention. |
| format | Article |
| id | doaj-art-06ffb8131e2544edb97b021c0138c6de |
| institution | OA Journals |
| issn | 2079-7737 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj-art-06ffb8131e2544edb97b021c0138c6de2025-08-20T02:33:38ZengMDPI AGBiology2079-77372025-05-0114550710.3390/biology14050507Targeting Methionine Metabolism Reveals AMPK-SAMTOR Signaling as a Therapeutic Vulnerability in Prostate CancerSerdar Arisan0Ayyuce Sever1Pinar Obakan-Yerlikaya2Elif Damla Arisan3Pinar Uysal-Onganer4Department of Urology, Hamidiye Medical School, Saglik Bilimleri University, 34700 Istanbul, TürkiyeInstitute of Biotechnology, Gebze Technical University, 41400 Kocaeli, TürkiyeDepartment of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Istanbul Medeniyet University, Uskudar, 34700 Istanbul, TürkiyeInstitute of Biotechnology, Gebze Technical University, 41400 Kocaeli, TürkiyeCancer Mechanisms and Biomarkers Research Group, School of Life Sciences, University of Westminster, London W1W 6UW, UKProstate cancer (PCa) is not only one of the most diagnosed malignancies in men but also a leading cause of cancer-related mortality globally. PCa exhibits unique metabolic dependencies, particularly on lipids and glutamine, unlike many solid tumors, rather than glycolysis. Methionine metabolism plays a crucial role in these metabolic pathways, contributing to polyamine biosynthesis, DNA methylation, and cellular signaling processes. Here, we demonstrate that methionine deprivation induces selective vulnerability in AMPK-deficient PC3 PCa cells by disrupting SAMTOR–mTOR signaling and triggering oxidative stress, lipid depletion, and autophagic responses. Through functional and proteomic analyses, we show that SAMTOR directly interacts with p-AMPK and modulates cell fate under methionine-limited conditions. Our findings establish a mechanistic link between methionine sensing and metabolic stress signaling in PCa, offering a new avenue for targeted intervention.https://www.mdpi.com/2079-7737/14/5/507mTORSAMTORmethionineprostate cancerautophagy |
| spellingShingle | Serdar Arisan Ayyuce Sever Pinar Obakan-Yerlikaya Elif Damla Arisan Pinar Uysal-Onganer Targeting Methionine Metabolism Reveals AMPK-SAMTOR Signaling as a Therapeutic Vulnerability in Prostate Cancer Biology mTOR SAMTOR methionine prostate cancer autophagy |
| title | Targeting Methionine Metabolism Reveals AMPK-SAMTOR Signaling as a Therapeutic Vulnerability in Prostate Cancer |
| title_full | Targeting Methionine Metabolism Reveals AMPK-SAMTOR Signaling as a Therapeutic Vulnerability in Prostate Cancer |
| title_fullStr | Targeting Methionine Metabolism Reveals AMPK-SAMTOR Signaling as a Therapeutic Vulnerability in Prostate Cancer |
| title_full_unstemmed | Targeting Methionine Metabolism Reveals AMPK-SAMTOR Signaling as a Therapeutic Vulnerability in Prostate Cancer |
| title_short | Targeting Methionine Metabolism Reveals AMPK-SAMTOR Signaling as a Therapeutic Vulnerability in Prostate Cancer |
| title_sort | targeting methionine metabolism reveals ampk samtor signaling as a therapeutic vulnerability in prostate cancer |
| topic | mTOR SAMTOR methionine prostate cancer autophagy |
| url | https://www.mdpi.com/2079-7737/14/5/507 |
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