{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:35:40Z","timestamp":1789986940595,"version":"4.0.1"},"reference-count":52,"publisher":"Bioscientifica","issue":"1","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:p>\n                    Primary cilia are sensory organelles involved in regulation of cellular signaling. Cilia loss is frequently observed in tumors; yet, the responsible mechanisms and consequences for tumorigenesis remain unclear. We demonstrate that cilia structure and function is disrupted in human pheochromocytomas \u2013 endocrine tumors of the adrenal medulla. This is concomitant with transcriptional changes within cilia-mediated signaling pathways that are associated with tumorigenesis generally and pheochromocytomas specifically. Importantly, cilia loss was most dramatic in patients with germline mutations in the pseudohypoxia-linked genes\n                    <jats:italic>SDHx<\/jats:italic>\n                    and\n                    <jats:italic>VHL<\/jats:italic>\n                    . Using a pheochromocytoma cell line derived from rat, we show that hypoxia and oncometabolite-induced pseudohypoxia are key drivers of cilia loss and identify that this is dependent on activation of an Aurora-A\/HDAC6 cilia resorption pathway. We also show cilia loss drives dramatic transcriptional changes associated with proliferation and tumorigenesis. Our data provide evidence for primary cilia dysfunction contributing to pathogenesis of pheochromocytoma by a hypoxic\/pseudohypoxic mechanism and implicates oncometabolites as ciliary regulators. This is important as pheochromocytomas can cause mortality by mechanisms including catecholamine production and malignant transformation, while hypoxia is a general feature of solid tumors. Moreover, pseudohypoxia-induced cilia resorption can be pharmacologically inhibited, suggesting potential for therapeutic intervention.\n                  <\/jats:p>","DOI":"10.1530\/erc-18-0134","type":"journal-article","created":{"date-parts":[[2018,9,7]],"date-time":"2018-09-07T06:50:16Z","timestamp":1536303016000},"page":"165-180","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":12,"title":["Oncometabolite induced primary cilia loss in pheochromocytoma"],"prefix":"10.1530","volume":"26","author":[{"given":"Samuel M","family":"O\u2019Toole","sequence":"first","affiliation":[{"name":"1William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK"},{"name":"2Department of Endocrinology, St Bartholomew\u2019s Hospital, Barts Health NHS Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S","family":"Watson","sequence":"additional","affiliation":[{"name":"1William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana V","family":"Novoselova","sequence":"additional","affiliation":[{"name":"1William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa E L","family":"Romano","sequence":"additional","affiliation":[{"name":"1William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J","family":"King","sequence":"additional","affiliation":[{"name":"1William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teisha Y","family":"Bradshaw","sequence":"additional","affiliation":[{"name":"1William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare L","family":"Thompson","sequence":"additional","affiliation":[{"name":"3Institute of Bioengineering and School of Engineering and Material Sciences, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin M","family":"Knight","sequence":"additional","affiliation":[{"name":"3Institute of Bioengineering and School of Engineering and Material Sciences, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyson V","family":"Sharp","sequence":"additional","affiliation":[{"name":"4Barts Cancer Institute, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R","family":"Barnes","sequence":"additional","affiliation":[{"name":"1William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umasuthan","family":"Srirangalingam","sequence":"additional","affiliation":[{"name":"1William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK"},{"name":"2Department of Endocrinology, St Bartholomew\u2019s Hospital, Barts Health NHS Trust, London, UK"},{"name":"5Department of Diabetes and Endocrinology, University College London Hospital, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M","family":"Drake","sequence":"additional","affiliation":[{"name":"2Department of Endocrinology, St Bartholomew\u2019s Hospital, Barts Health NHS Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Paul","family":"Chapple","sequence":"additional","affiliation":[{"name":"1William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref241","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1530\/ERC-13-0494","article-title":"Pathological grading for predicting metastasis in phaeochromocytoma and paraganglioma","volume":"21","year":"2014","journal-title":"Endocrine-Related Cancer"},{"key":"ref431","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/modpathol.2008.132","article-title":"Sporadic clear cell renal cell carcinoma but not the papillary type is characterized by severely reduced frequency of primary cilia","volume":"22","year":"2009","journal-title":"Modern Pathology"},{"key":"ref301","first-page":"114","article-title":"All Along the 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