{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T13:50:17Z","timestamp":1780408217784,"version":"3.54.1"},"posted":{"date-parts":[[2025,12,27]]},"group-title":"Cell Biology","reference-count":96,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T00:00:00Z","timestamp":1766793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH","award":["R01 CA173481"],"award-info":[{"award-number":["R01 CA173481"]}]},{"name":"NIH","award":["R01 CA183929"],"award-info":[{"award-number":["R01 CA183929"]}]},{"name":"NIH","award":["P01 CA265768"],"award-info":[{"award-number":["P01 CA265768"]}]},{"name":"NIH","award":["P30 CA013696"],"award-info":[{"award-number":["P30 CA013696"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Metastasis\u2014the process by which cancer cells spread beyond the primary tumor to distant organs\u2014accounts for the vast majority of cancer-related deaths. To elucidate mechanisms underlying dissemination and metastasis in prostate cancer, we have investigated circulating tumor cells (CTCs) obtained from genetically engineered mouse models (GEMMs). The phenotypic and molecular properties of the CTCs, and organoids derived from these CTCs, closely model the tumor and metastatic phenotypes of their parental GEMMs. Moreover, organoids derived from individual CTCs exhibit molecular and morphological heterogeneity that is associated with distinct metabolic states as well as differences in human prostate cancer outcome. Using computational systems analyses, we have identified\n                  <jats:italic>TMPO<\/jats:italic>\n                  , encoding the nuclear membrane protein lamina-associated polypeptide 2 (Lap2), as a key driver of this heterogeneity.\n                  <jats:italic>TMPO<\/jats:italic>\n                  activity is upregulated in advanced human prostate tumors, metastases, and CTCs, and is associated with adverse clinical outcome. Our findings indicate that\n                  <jats:italic>TMPO<\/jats:italic>\n                  promotes dissemination and metastasis\n                  <jats:italic>in vivo<\/jats:italic>\n                  by enhancing survival in conditions of metabolic stress, and reveal a novel mechanistic link between CTC heterogeneity, stress adaptation, and metastatic potential.\n                <\/jats:p>","DOI":"10.64898\/2025.12.27.696673","type":"posted-content","created":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T02:00:15Z","timestamp":1766887215000},"source":"Crossref","is-referenced-by-count":1,"title":["TMPO promotes cellular dissemination and metastasis in circulating tumor cells"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5874-1851","authenticated-orcid":false,"given":"Arianna","family":"Giacobbe","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology and Therapeutics, Columbia University, Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandar Z.","family":"Obradovic","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Columbia University, Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA"},{"name":"Department of Medicine, Columbia University, Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinqiu","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Columbia University, Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA"},{"name":"Department of Medicine, Columbia University, Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA"},{"name":"Department of Genetics & Development, Columbia University, Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA"},{"name":"Department of Urology, Columbia 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