{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:20:07Z","timestamp":1792790407318,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,16]]},"group-title":"Cell Biology","reference-count":51,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["BB\/V003178\/1"],"award-info":[{"award-number":["BB\/V003178\/1"]}],"id":[{"id":"https:\/\/ror.org\/00cwqg982","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Republic of Turkey Ministry of National Education","award":["Selection and Placement of Candidates Sent Abroad for Postgraduate Education (YLSY) scholarship program - Merve Kocbiyik"],"award-info":[{"award-number":["Selection and Placement of Candidates Sent Abroad for Postgraduate Education (YLSY) scholarship program - Merve Kocbiyik"]}],"id":[{"id":"https:\/\/ror.org\/00jga9g46","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Commonwealth Scholarship Commission and the Foreign, Commonwealth and Development Office in the UK","award":["Afshan Afzal"],"award-info":[{"award-number":["Afshan Afzal"]}],"id":[{"id":"https:\/\/ror.org\/037wke960","id-type":"ROR","asserted-by":"crossref"}]},{"name":"American Thyroid Association","award":["ThyCa Research Grant"],"award-info":[{"award-number":["ThyCa Research Grant"]}],"id":[{"id":"https:\/\/ror.org\/00nhwe772","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Society for Endocrinology","award":["Early Career Grant"],"award-info":[{"award-number":["Early Career Grant"]}],"id":[{"id":"https:\/\/ror.org\/04k6mn280","id-type":"ROR","asserted-by":"crossref"}]},{"name":"British Thyroid Foundation","award":["BTF Research Award"],"award-info":[{"award-number":["BTF Research Award"]}],"id":[{"id":"https:\/\/ror.org\/05af1hn65","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,16]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Directional cell migration requires cells to sense extracellular cues and coordinate adhesion, cytoskeletal remodelling and polarity, yet the molecular regulators that integrate these events remain incompletely defined. PTTG1-binding factor (PBF\/PTTG1IP) is a transmembrane glycoprotein extensively characterised in pathological overexpression and cancer models, where elevated expression promotes tumourigenic cellular phenotypes. However, its endogenous physiological function remains poorly understood. Here, separate enrichment analyses of transcriptomic and phosphoproteomic profiles from PBF-overexpressing cells collectively highlighted cell adhesion, extracellular matrix organisation, cytoskeletal regulation and cell motility as major PBF-associated programmes. Using a novel Pbf knockout mouse model, we show that primary Pbf-KO mouse embryonic fibroblasts exhibit impaired migration and invasion. PBF loss reduced fibronectin adhesion, disrupted focal adhesion number, size and distribution, attenuated FAK Tyr397 phosphorylation and delayed early adhesion formation. Live-cell imaging and Golgi orientation assays further revealed altered actin organisation and impaired front\u2013rear polarity in Pbf-KO cells. Key phenotypes were conserved in CRISPR\u2013Cas9 PBF-KO human thyroid cancer cells, while targeted PBF re-expression restored migration in Pbf-KO MEFs. We thus identify PBF as an endogenous regulator of cell adhesion, polarity and directional motility, providing a framework for understanding how pathological PBF overexpression may promote invasive behaviour in cancer.<\/jats:p>","DOI":"10.64898\/2026.09.14.751110","type":"posted-content","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:30:34Z","timestamp":1789619434000},"source":"Crossref","is-referenced-by-count":0,"title":["PBF\/PTTG1IP coordinates focal adhesion formation, polarity and cell motility"],"prefix":"10.64898","author":[{"given":"Merve","family":"Kocbiyik","sequence":"first","affiliation":[{"name":"Department of Metabolism & Systems Science (MSS) and Centre for Endocrinology, Diabetes and Metabolism (CEDAM), College of Medicine and Health, University of Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selvambigai","family":"Manivannan","sequence":"additional","affiliation":[{"name":"Department of Metabolism & Systems Science (MSS) and Centre for Endocrinology, Diabetes and Metabolism (CEDAM), College of Medicine and Health, University of Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davina","family":"Banga","sequence":"additional","affiliation":[{"name":"Department of Metabolism & Systems Science (MSS) and Centre for Endocrinology, Diabetes and Metabolism (CEDAM), College of Medicine and Health, University of Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditi","family":"Hariharan","sequence":"additional","affiliation":[{"name":"Department of Metabolism & Systems Science (MSS) and Centre for Endocrinology, Diabetes and Metabolism (CEDAM), College of Medicine and Health, University of Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed E","family":"El-Asrag","sequence":"additional","affiliation":[{"name":"Aston Medical School, College of Health and Life Sciences, Aston University, Birmingham, UK"},{"name":"Faculty of Science, Benha University, Benha, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0784-2967","authenticated-orcid":false,"given":"Andrew D","family":"Beggs","sequence":"additional","affiliation":[{"name":"Department of Cancer and Genomic Sciences (CGS), College of Medicine and Health, University of Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paloma","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Cancer and Genomic Sciences (CGS), College of Medicine and Health, University of Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean P","family":"Larner","sequence":"additional","affiliation":[{"name":"Department of Metabolism & Systems Science (MSS) and Centre for Endocrinology, Diabetes and Metabolism (CEDAM), College of Medicine and Health, University of Birmingham, 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