{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:24:34Z","timestamp":1793147074511,"version":"4.5.0"},"reference-count":52,"publisher":"National Academy of Sciences","issue":"13","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82573804"],"award-info":[{"award-number":["82573804"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82103194"],"award-info":[{"award-number":["82103194"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,3,31]]},"abstract":"<jats:p>\n                    Metabolic reprogramming is a fundamental hallmark of cancer progression. However, the oncogenic mechanisms underlying serine metabolism and its impact on chemotherapeutic sensitivity in gastric cancer (GC) remain poorly defined. Here, through integrated metabolomics and\n                    <jats:sup>13<\/jats:sup>\n                    C-labeled metabolic flux analysis, we identify marked dysregulation of serine metabolism in GC, primarily driven by increased expression of phosphoglycerate dehydrogenase (PHGDH). Mechanistically, we show that with no lysine kinase 1 (WNK1) phosphorylates PHGDH at Ser349 and Ser371, enhancing its enzymatic activity and protein stability by preventing ubiquitin-mediated degradation. In vivo, WNK1 knockout mice exhibit significantly reduced gastric tumor burden, accompanied by decreased serine levels and disrupted redox balance, supporting the protumorigenic role of the WNK1\u2013PHGDH axis. Clinically, enhanced PHGDH activity, elevated serine levels, and increased glutathione abundance are strongly associated with poor oxaliplatin response in GC patient cohorts, suggesting PHGDH as a potential predictive biomarker for chemotherapy resistance. Together, these findings delineate a WNK1\u2013PHGDH\u2013driven serine metabolic reprogramming axis that promotes redox adaptation and chemoresistance in GC, highlighting its dual value as a mechanistic driver and a therapeutic vulnerability in cancer treatment.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2525213123","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T18:07:16Z","timestamp":1774462036000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":4,"title":["PHGDH phosphorylation mediated by WNK1 serves as a dual marker of metabolic vulnerability and responsiveness to oxaliplatin treatment"],"prefix":"10.1073","volume":"123","author":[{"given":"Shaobo","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Radiology, Zhengzhou University People\u2019s Hospital & Henan Provincial People\u2019s Hospital","place":["Zhengzhou, China"]},{"name":"China-United States 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Institute of Advanced Biomedical Sciences, Zhengzhou University","place":["Zhengzhou, Henan, China"]},{"name":"Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengjuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Shao","sequence":"additional","affiliation":[{"name":"China-United States (Henan) Hormel Cancer Institute","place":["Jinshui District, Zhengzhou, China"]},{"name":"Henan Key Laboratory of Chronic Disease Management, Fuwai Central China Cardiovascular Hospital","place":["Zhengzhou, China"]},{"name":"Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou 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