{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:35:55Z","timestamp":1785429355970,"version":"3.56.0"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Telethon","award":["GGP15219"],"award-info":[{"award-number":["GGP15219"]}]},{"name":"Piano per lo Sviluppo della Ricerca (PSR), F-DIP, University of Siena","award":["XXX"],"award-info":[{"award-number":["XXX"]}]},{"award":["XXX"],"award-info":[{"award-number":["XXX"]}],"id":[{"id":"https:\/\/ror.org\/01tevnk56","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>K-Rev Interaction Trapped protein-1 (KRIT1) is a scaffold protein that forms functional protein complexes involved in physiologically important signaling networks. While it is primarily recognized for its association with Cerebral Cavernous Malformations (CCMs), KRIT1 may also play critical roles in tumor formation and the acquisition of malignant phenotypes, regulating cell adhesion, cytoskeletal dynamics, and angiogenesis. In this study, we investigated the role of KRIT1 in cancer cell migration and metastasis, with a focus on identifying novel interacting proteins and characterizing the intracellular signaling pathways activated upon its loss. By using a yeast two-hybrid screening, we identified Kinesin Family Member 1C (KIF1C), a protein involved in regulating podosome and invadopodium elongation, as a novel binding partner of KRIT1, and the interaction was confirmed in melanoma and epithelial cancer cells. In silico docking and interaction interface analyses supported the KRIT1\u2013KIF1C interaction, providing structural insight into the binding mode as shown experimentally. We also found that SRC and focal adhesion kinase (FAK) phosphorylation, as well as Ras homolog family member A (RhoA) expression, represent additional pathways affected by the loss of KRIT1. This study confirms our earlier hypothesis that KRIT1 functions as a tumor suppressor and uncovers a compelling link between its loss and enhanced cancer aggressiveness.<\/jats:p>","DOI":"10.3390\/ijms27083419","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T13:16:17Z","timestamp":1775826977000},"page":"3419","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unveiling a Novel Molecular Interaction and Pro-Metastatic Signaling Cascades Driven by KRIT1"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4998-2268","authenticated-orcid":false,"given":"Lucrezia","family":"Paradisi","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Guazzi","sequence":"additional","affiliation":[{"name":"HansaBioMed Life Sciences Ltd., 12618 Tallinn, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6862-1732","authenticated-orcid":false,"given":"Matteo","family":"Macis","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Finetti","sequence":"additional","affiliation":[{"name":"Department of Life Science, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Trezza","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9151-2866","authenticated-orcid":false,"given":"Raffaella","family":"De Paolo","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology (IFC), Italian National Research Council (CNR), Via Moruzzi 1, 56124 Pisa, Italy"},{"name":"Oncogenomics Unit, Core Research Laboratory (CRL), Institute for the Study, Prevention and Oncology Network (ISPRO), Via Moruzzi 1, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0237-4359","authenticated-orcid":false,"given":"Marta","family":"Roncetti","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology (IFC), Italian National Research Council (CNR), Via Moruzzi 1, 56124 Pisa, Italy"},{"name":"Oncogenomics Unit, Core Research Laboratory (CRL), Institute for the Study, Prevention and Oncology Network (ISPRO), Via Moruzzi 1, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Marshall","sequence":"additional","affiliation":[{"name":"Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6557-955X","authenticated-orcid":false,"given":"Laura","family":"Poliseno","sequence":"additional","affiliation":[{"name":"Institute of Clinical Physiology (IFC), Italian National Research Council (CNR), Via Moruzzi 1, 56124 Pisa, Italy"},{"name":"Oncogenomics Unit, Core Research Laboratory (CRL), Institute for the Study, Prevention and Oncology Network (ISPRO), Via Moruzzi 1, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1144-3360","authenticated-orcid":false,"given":"Federica","family":"Finetti","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0850-7186","authenticated-orcid":false,"given":"Lorenza","family":"Trabalzini","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/s41392-025-02148-4","article-title":"Invasion and Metastasis in Cancer: Molecular Insights and Therapeutic Targets","volume":"10","author":"Li","year":"2025","journal-title":"Signal Transduct. 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