{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:51:20Z","timestamp":1786978280540,"version":"build-2736575974"},"reference-count":60,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T00:00:00Z","timestamp":1663027200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Thyroid cancer is associated with genetic alterations, e.g. BRAF\n                    <jats:sup>V600E<\/jats:sup>\n                    , which may cause carcinomatous changes in hormone\u2010secreting epithelial cells. Epidemiological studies have shown that overnutrition is related to the development and progression of cancer. In this study, we attempted to identify the cell nonautonomous factor responsible for the progression of BRAF\n                    <jats:sup>V600E<\/jats:sup>\n                    thyroid cancer under overnutrition conditions. We developed a mouse model for inducible thyrocyte\u2010specific activation of BRAF\n                    <jats:sup>V600E<\/jats:sup>\n                    , which showed features similar to those of human papillary thyroid cancer.\n                    <jats:italic>LSL\u2010Braf<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>V600E<\/jats:italic>\n                    <\/jats:sup>\n                    ;\n                    <jats:italic>Tg<\/jats:italic>\n                    CreER\n                    <jats:sup>T2<\/jats:sup>\n                    showed thyroid tumour development in the entire thyroid, and the tumour showed more abnormal cellular features with mitochondrial abnormalities in mice fed a high\u2010fat diet (HFD). Transcriptomics revealed that adrenomedullin2 (\n                    <jats:italic>Adm2<\/jats:italic>\n                    ) was increased in\n                    <jats:italic>LSL\u2010Braf<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>V600E<\/jats:italic>\n                    <\/jats:sup>\n                    ;\n                    <jats:italic>Tg<\/jats:italic>\n                    CreER\n                    <jats:sup>T2<\/jats:sup>\n                    mice fed HFD.\n                    <jats:italic>ADM2<\/jats:italic>\n                    was upregulated on the addition of a mitochondrial complex I inhibitor or palmitic acid with integrated stress response (ISR) in cancer cells. ADM2 stimulated protein kinase A and extracellular signal\u2010regulated kinase\n                    <jats:italic>in vitro<\/jats:italic>\n                    . The knockdown of\n                    <jats:italic>ADM2<\/jats:italic>\n                    suppressed the proliferation and migration of thyroid cancer cells. We searched The Cancer Genome Atlas and Genotype\u2010Tissue Expression databases and found that increased\n                    <jats:italic>ADM2<\/jats:italic>\n                    expression was associated with ISR and poor overall survival. Consistently, upregulated\n                    <jats:italic>ADM2<\/jats:italic>\n                    expression in tumour cells and circulating ADM2 molecules were associated with aggressive clinicopathological parameters, including body mass index, in thyroid cancer patients. Collectively, we identified that ADM2 is released from cancer cells under mitochondrial stress resulting from overnutrition and acts as a secretory factor determining the progressive properties of thyroid cancer. \u00a9 2022 The Authors.\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.5997","type":"journal-article","created":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T23:54:57Z","timestamp":1659657297000},"page":"264-277","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Adrenomedullin2 stimulates progression of thyroid cancer in mice and humans under nutrient excess conditions"],"prefix":"10.1002","volume":"258","author":[{"given":"Jung Tae","family":"Kim","sequence":"first","affiliation":[{"name":"Research Center for Endocrine and Metabolic Diseases Chungnam National University School of Medicine  Daejeon Republic of Korea"},{"name":"Department of Medical Science Chungnam National University School of Medicine  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi Ae","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Chungnam National University School of Medicine  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong Eun","family":"Lee","sequence":"additional","affiliation":[{"name":"Research Center for Endocrine and Metabolic Diseases Chungnam National University School of Medicine  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Science and Engineering Korea Advanced Institute of Science and Technology (KAIST)  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Yong","family":"Koh","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Science and Engineering Korea Advanced Institute of Science and Technology (KAIST)  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Science and Engineering Korea Advanced Institute of Science and Technology (KAIST)  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Mi","family":"Jun","sequence":"additional","affiliation":[{"name":"Center for Research Equipment Korea Basic Science Institute  Cheongju Republic of Korea"},{"name":"Convergent Research Center for Emerging Virus Infection Korea Research Institute of Chemical Technology  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Man","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology Chungnam National University School of Medicine  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun Ho","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine Chungnam National University School of Medicine  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo Shik","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Seoul National University College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7394-3830","authenticated-orcid":false,"given":"Sun Wook","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Seoul National University College of Medicine  Seoul Republic of Korea"},{"name":"Department of Internal Medicine Seoul National University Hospital  Seoul Republic of Korea"},{"name":"Cellus Inc.  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