{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T23:17:29Z","timestamp":1785799049849,"version":"3.56.0"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82403650"],"award-info":[{"award-number":["82403650"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82172922"],"award-info":[{"award-number":["82172922"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772934"],"award-info":[{"award-number":["81772934"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023TQ0141"],"award-info":[{"award-number":["2023TQ0141"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Young Talent Fund of Association for Science and Technology in Shaanxi"},{"name":"State Key Laboratory of Cancer Biology Project"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sig Transduct Target Ther"],"DOI":"10.1038\/s41392-026-02733-1","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:49:45Z","timestamp":1781585385000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["AKAP1 enhances glycogen accumulation and hepatocarcinogenesis through YTHDF2-mediated G6PC mRNA decay"],"prefix":"10.1038","volume":"11","author":[{"given":"Tao","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zifeng","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shixia","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyu","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weifang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuyang","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jibin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinliang","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"2733_CR1","doi-asserted-by":"publisher","first-page":"6133","DOI":"10.3390\/ijms24076133","volume":"24","author":"GST Soon","year":"2023","unstructured":"Soon, G. S. T. & Torbenson, M. The liver and glycogen: in sickness and in health. Int J. Mol. Sci. 24, 6133 (2023).","journal-title":"Int J. Mol. Sci."},{"key":"2733_CR2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202216029","volume":"14","author":"LEA Young","year":"2022","unstructured":"Young, L. E. A. et al. In situ mass spectrometry imaging reveals heterogeneous glycogen stores in human normal and cancerous tissues. EMBO Mol. Med. 14, e16029 (2022).","journal-title":"EMBO Mol. Med."},{"key":"2733_CR3","doi-asserted-by":"publisher","first-page":"5559","DOI":"10.1016\/j.cell.2021.10.001","volume":"184","author":"Q Liu","year":"2021","unstructured":"Liu, Q. et al. Glycogen accumulation and phase separation drives liver tumor initiation. Cell 184, 5559\u20135576.e5519 (2021).","journal-title":"Cell"},{"key":"2733_CR4","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/s00109-015-1377-9","volume":"94","author":"CE Zois","year":"2016","unstructured":"Zois, C. E. & Harris, A. L. Glycogen metabolism has a key role in the cancer microenvironment and provides new targets for cancer therapy. J. Mol. Med. 94, 137\u2013154 (2016).","journal-title":"J. Mol. Med."},{"key":"2733_CR5","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.cmet.2018.08.007","volume":"29","author":"M Curtis","year":"2019","unstructured":"Curtis, M. et al. Fibroblasts mobilize tumor cell glycogen to promote proliferation and metastasis. Cell Metab. 29, 141\u2013155.e149 (2019).","journal-title":"Cell Metab."},{"key":"2733_CR6","doi-asserted-by":"publisher","first-page":"298","DOI":"10.3390\/cells9020298","volume":"9","author":"Y Liu","year":"2020","unstructured":"Liu, Y., Merrill, R. A. & Strack, S. A-kinase anchoring protein 1: emerging roles in regulating mitochondrial form and function in health and disease. Cells 9, 298 (2020).","journal-title":"Cells"},{"key":"2733_CR7","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1007\/s00125-020-05103-w","volume":"63","author":"B Qi","year":"2020","unstructured":"Qi, B. et al. Akap1 deficiency exacerbates diabetic cardiomyopathy in mice by NDUFS1-mediated mitochondrial dysfunction and apoptosis. Diabetologia 63, 1072\u20131087 (2020).","journal-title":"Diabetologia"},{"key":"2733_CR8","doi-asserted-by":"publisher","first-page":"4026","DOI":"10.7150\/ijbs.73493","volume":"18","author":"J Feng","year":"2022","unstructured":"Feng, J. et al. AKAP1 contributes to impaired mtDNA replication and mitochondrial dysfunction in podocytes of diabetic kidney disease. Int J. Biol. Sci. 18, 4026\u20134042 (2022).","journal-title":"Int J. Biol. Sci."},{"key":"2733_CR9","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202002794","volume":"8","author":"L Ji","year":"2021","unstructured":"Ji, L. et al. AKAP1 deficiency attenuates diet-induced obesity and insulin resistance by promoting fatty acid oxidation and thermogenesis in brown adipocytes. Adv. Sci. 8, 2002794 (2021).","journal-title":"Adv. Sci."},{"key":"2733_CR10","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.241","volume":"8","author":"L Rinaldi","year":"2017","unstructured":"Rinaldi, L. et al. Mitochondrial AKAP1 supports mTOR pathway and tumor growth. Cell Death Dis. 8, e2842 (2017).","journal-title":"Cell Death Dis."},{"key":"2733_CR11","doi-asserted-by":"publisher","first-page":"434","DOI":"10.3892\/ol.2021.12695","volume":"21","author":"N Yang","year":"2021","unstructured":"Yang, N. et al. Epigenetic silencing of microRNA-199a-5p promotes the proliferation of non-small cell lung cancer cells by increasing AKAP1 expression. Oncol. Lett. 21, 434 (2021).","journal-title":"Oncol. Lett."},{"key":"2733_CR12","first-page":"131","volume":"16","author":"J Yu","year":"2018","unstructured":"Yu, J., Zhang, Y., Zhou, D., Wu, J. & Luo, R. Higher expression of A-kinase anchoring-protein 1 predicts poor prognosis in human hepatocellular carcinoma. Oncol. Lett. 16, 131\u2013136 (2018).","journal-title":"Oncol. Lett."},{"key":"2733_CR13","doi-asserted-by":"publisher","first-page":"8233","DOI":"10.1523\/JNEUROSCI.0649-18.2018","volume":"38","author":"KH Flippo","year":"2018","unstructured":"Flippo, K. H. et al. AKAP1 protects from cerebral ischemic stroke by inhibiting Drp1-dependent mitochondrial fission. J. Neurosci. 38, 8233\u20138242 (2018).","journal-title":"J. Neurosci."},{"key":"2733_CR14","doi-asserted-by":"publisher","first-page":"113512","DOI":"10.1016\/j.yexcr.2023.113512","volume":"424","author":"X Li","year":"2023","unstructured":"Li, X., Yang, Q., Liu, S., Song, S. & Wang, C. Mitochondria-associated endoplasmic reticulum membranes promote mitochondrial fission through AKAP1-Drp1 pathway in podocytes under high glucose conditions. Exp. Cell Res. 424, 113512 (2023).","journal-title":"Exp. Cell Res."},{"key":"2733_CR15","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s40164-022-00269-y","volume":"11","author":"X Chen","year":"2022","unstructured":"Chen, X., Zhou, X. & Wang, X. m(6)A binding protein YTHDF2 in cancer. Exp. Hematol. Oncol. 11, 21 (2022).","journal-title":"Exp. Hematol. Oncol."},{"key":"2733_CR16","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1097\/HEP.0000000000000786","volume":"82","author":"X Wang","year":"2025","unstructured":"Wang, X., Zhang, L. & Dong, B. Molecular mechanisms in MASLD\/MASH-related HCC. Hepatology 82, 1303\u20131324 (2025).","journal-title":"Hepatology"},{"key":"2733_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-58790-7","volume":"16","author":"L He","year":"2025","unstructured":"He, L. et al. Hepatic AKAP1 deficiency exacerbates diet-induced MASLD by enhancing GPAT1-mediated lysophosphatidic acid synthesis. Nat. Commun. 16, 4286 (2025).","journal-title":"Nat. Commun."},{"key":"2733_CR18","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.neo.2022.01.001","volume":"25","author":"DS Chandrashekar","year":"2022","unstructured":"Chandrashekar, D. S. et al. UALCAN: an update to the integrated cancer data analysis platform. Neoplasia 25, 18\u201327 (2022).","journal-title":"Neoplasia"},{"key":"2733_CR19","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-025-06314-8","volume":"23","author":"D Li","year":"2025","unstructured":"Li, D. et al. MAZ-mediated N6-methyladenosine modification of ZEB1 promotes hepatocellular carcinoma progression by regulating METTL3. J. Transl. Med. 23, 265 (2025).","journal-title":"J. Transl. Med."},{"key":"2733_CR20","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.3390\/ijms23031155","volume":"23","author":"J Gyamfi","year":"2022","unstructured":"Gyamfi, J., Kim, J. & Choi, J. Cancer as a metabolic disorder. Int J. Mol. Sci. 23, 1155 (2022).","journal-title":"Int J. Mol. Sci."},{"key":"2733_CR21","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1080\/09553002.2022.2113837","volume":"99","author":"A Tsolou","year":"2023","unstructured":"Tsolou, A., Koparanis, D., Lamprou, I., Giatromanolaki, A. & Koukourakis, M. I. Increased glucose influx and glycogenesis in lung cancer cells surviving after irradiation. Int J. Radiat. Biol. 99, 692\u2013701 (2023).","journal-title":"Int J. Radiat. Biol."},{"key":"2733_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06202-3","volume":"14","author":"S Hasani","year":"2023","unstructured":"Hasani, S. et al. Inhibition of mitochondrial fission activates glycogen synthesis to support cell survival in colon cancer. Cell Death Dis. 14, 664 (2023).","journal-title":"Cell Death Dis."},{"key":"2733_CR23","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/j.trecan.2019.05.003","volume":"5","author":"P Dauer","year":"2019","unstructured":"Dauer, P. & Lengyel, E. New roles for glycogen in tumor progression. Trends Cancer 5, 396\u2013399 (2019).","journal-title":"Trends Cancer"},{"key":"2733_CR24","doi-asserted-by":"publisher","first-page":"2882","DOI":"10.1111\/febs.70040","volume":"292","author":"A Theodoulou","year":"2025","unstructured":"Theodoulou, A. et al. Stbd1 stimulates AMPK signaling and alleviates insulin resistance in an in vitro hepatocyte model. FEBS J. 292, 2882\u20132901 (2025).","journal-title":"FEBS J."},{"key":"2733_CR25","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1016\/j.ccell.2023.04.019","volume":"41","author":"L Wang","year":"2023","unstructured":"Wang, L. et al. YTHDF2 inhibition potentiates radiotherapy antitumor efficacy. Cancer Cell 41, 1294\u20131308.e1298 (2023).","journal-title":"Cancer Cell"},{"key":"2733_CR26","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-020-01267-6","volume":"19","author":"J Li","year":"2020","unstructured":"Li, J. et al. YTHDF2 mediates the mRNA degradation of the tumor suppressors to induce AKT phosphorylation in N6-methyladenosine-dependent way in prostate cancer. Mol. Cancer 19, 152 (2020).","journal-title":"Mol. Cancer"},{"key":"2733_CR27","doi-asserted-by":"publisher","first-page":"2254","DOI":"10.1002\/hep.29683","volume":"67","author":"M Chen","year":"2018","unstructured":"Chen, M. et al. RNA N6-methyladenosine methyltransferase-like 3 promotes liver cancer progression through YTHDF2-dependent posttranscriptional silencing of SOCS2. Hepatology 67, 2254\u20132270 (2018).","journal-title":"Hepatology"},{"key":"2733_CR28","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1158\/2159-8290.CD-20-0331","volume":"11","author":"D Dixit","year":"2021","unstructured":"Dixit, D. et al. The RNA m6A Reader YTHDF2 maintains oncogene expression and is a targetable dependency in glioblastoma stem cells. Cancer Discov. 11, 480\u2013499 (2021).","journal-title":"Cancer Discov."},{"key":"2733_CR29","doi-asserted-by":"publisher","first-page":"2859","DOI":"10.1093\/nar\/gkab065","volume":"49","author":"G Hou","year":"2021","unstructured":"Hou, G. et al. SUMOylation of YTHDF2 promotes mRNA degradation and cancer progression by increasing its binding affinity with m6A-modified mRNAs. Nucleic Acids Res. 49, 2859\u20132877 (2021).","journal-title":"Nucleic Acids Res."},{"key":"2733_CR30","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/s41392-023-01316-8","volume":"8","author":"Y Yang","year":"2023","unstructured":"Yang, Y. et al. O-GlcNAcylation of YTHDF2 promotes HBV-related hepatocellular carcinoma progression in an N(6)-methyladenosine-dependent manner. Signal Transduct. Target Ther. 8, 63 (2023).","journal-title":"Signal Transduct. Target Ther."},{"key":"2733_CR31","doi-asserted-by":"publisher","DOI":"10.1126\/science.adi3332","volume":"383","author":"J Chen","year":"2024","unstructured":"Chen, J. et al. Hepatic glycogenesis antagonizes lipogenesis by blocking S1P via UDPG. Science 383, eadi3332 (2024).","journal-title":"Science"},{"key":"2733_CR32","doi-asserted-by":"publisher","DOI":"10.34133\/research.0184","volume":"6","author":"H Zhang","year":"2023","unstructured":"Zhang, H. et al. NOP2-mediated m5C modification of c-Myc in an EIF3A-dependent manner to reprogram glucose metabolism and promote hepatocellular carcinoma progression. Research 6, 0184 (2023).","journal-title":"Research"},{"key":"2733_CR33","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1038\/sj.onc.1201283","volume":"15","author":"M Komatsu","year":"1997","unstructured":"Komatsu, M. et al. MAZ, a Myc-associated zinc finger protein, is essential for the ME1a1-mediated expression of the c-myc gene during neuroectodermal differentiation of P19 cells. Oncogene 15, 1123\u20131131 (1997).","journal-title":"Oncogene"},{"key":"2733_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109660","volume":"115","author":"M Wang","year":"2023","unstructured":"Wang, M. et al. Comprehensive analysis of the tumor-promoting effect and immune infiltration correlation MAZ from pan-cancer to hepatocellular carcinoma. Int. Immunopharmacol. 115, 109660 (2023).","journal-title":"Int. Immunopharmacol."},{"key":"2733_CR35","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1002\/cam4.362","volume":"4","author":"A Ray","year":"2015","unstructured":"Ray, A. & Ray, B. K. Induction of Ras by SAF-1\/MAZ through a feed-forward loop promotes angiogenesis in breast cancer. Cancer Med. 4, 224\u2013234 (2015).","journal-title":"Cancer Med."},{"key":"2733_CR36","doi-asserted-by":"publisher","first-page":"2639","DOI":"10.1096\/fj.11-202820","volume":"26","author":"M Smits","year":"2012","unstructured":"Smits, M. et al. Myc-associated zinc finger protein (MAZ) is regulated by miR-125b and mediates VEGF-induced angiogenesis in glioblastoma. FASEB J. 26, 2639\u20132647 (2012).","journal-title":"FASEB J."},{"key":"2733_CR37","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1016\/j.jhep.2021.01.028","volume":"74","author":"L Conde de la Rosa","year":"2021","unstructured":"Conde de la Rosa, L. et al. STARD1 promotes NASH-driven HCC by sustaining the generation of bile acids through the alternative mitochondrial pathway. J. Hepatol. 74, 1429\u20131441 (2021).","journal-title":"J. Hepatol."},{"key":"2733_CR38","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1016\/j.ajpath.2013.12.002","volume":"184","author":"X Chen","year":"2014","unstructured":"Chen, X. & Calvisi, D. F. Hydrodynamic transfection for generation of novel mouse models for liver cancer research. Am. J. Pathol. 184, 912\u2013923 (2014).","journal-title":"Am. J. Pathol."},{"key":"2733_CR39","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2023.155628","volume":"147","author":"T Yang","year":"2023","unstructured":"Yang, T. et al. OCTN2 enhances PGC-1\u03b1-mediated fatty acid oxidation and OXPHOS to support stemness in hepatocellular carcinoma. Metabolism 147, 155628 (2023).","journal-title":"Metabolism"},{"key":"2733_CR40","doi-asserted-by":"crossref","unstructured":"Lu, S. et al. RNA N(6)-methyladenosine reader protein YTHDF1 promotes plasma cell differentiation via IRF4 regulation in systemic lupus erythematosus. Exp. Mol. Med. 57, 2574\u20132587 (2025).","DOI":"10.1038\/s12276-025-01587-x"}],"container-title":["Signal Transduction and Targeted Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02733-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02733-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02733-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:49:53Z","timestamp":1781585393000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02733-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,16]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2733"],"URL":"https:\/\/doi.org\/10.1038\/s41392-026-02733-1","relation":{},"ISSN":["2059-3635"],"issn-type":[{"value":"2059-3635","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,16]]},"assertion":[{"value":"17 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 March 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 April 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"236"}}