{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:14:46Z","timestamp":1790014486157,"version":"4.0.1"},"reference-count":84,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020581","name":"Fondazione AIRC per la ricerca sul cancro ETS","doi-asserted-by":"publisher","award":["32438"],"award-info":[{"award-number":["32438"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>High\u2011risk (HR) human papillomaviruses (HPVs) rely on the continuous expression of the E6 and E7 oncoproteins to reshape epithelial biology, drive and sustain malignant transformation. The high\u2011risk E7 oncoprotein is multifunctional, and its phosphorylation by Casein Kinase II (CKII) is a key post translational modification that amplifies its oncogenic potential. Therefore, it is important to extensively delineate the consequences of E7 phosphorylation on HPV-driven transformation and malignant progression. Here, we identify Vangl1, a core planar cell polarity (PCP) scaffold protein, as a novel, phosphorylation\u2011dependent interactor of HPV\u201116 E7. Through proteomics, biochemical and cell-based assays, this study established that CKII\u2011mediated phosphorylation is required for Vangl1 recruitment, and that this interaction is more pronounced with HPV\u201116 E7, revealing a new mechanism by which HR HPVs might disrupt epithelial organization. In CaSki cells and ectopic expression models, E7 expression profoundly disrupts Vangl1 homeostasis, creating a biphasic proteostatic imbalance in which phosphorylated Vangl1 is aberrantly stabilised. This retention parallels E7 stability, revealing a reciprocal oncogenic stabilization. Furthermore, we found that Vangl1 is depleted in cytoskeletal cell fractions in the presence of E7, and that E7 translocates to membrane compartments where it colocalizes with Vangl1. In line with this, we identified that this abnormal Vangl1 stabilization occurs from its mislocalization and impaired trafficking arising from E7\u2019s interference with the Adaptor-Related Protein Complex 1 Subunit Mu 1 (AP1M1). Functionally, Vangl1 siRNA-mediated ablation in CaSki spheroids mirrors E6\/E7 loss, leading to disrupted spheroidal architecture, reduced invasion, and increased sensitivity to chemotherapeutic stress. These phenotypes position Vangl1 as a key downstream effector through which E7 reshaped epithelial behaviour. Taken together, our findings reveal a CKII-dependent mechanism by which HPV-16 E7 hijacks a core planar polarity component to destabilize epithelial structure and promote malignant traits; thus, positioning Vangl1 as a potential druggable target in HPV-associated cervical cancer.<\/jats:p>","DOI":"10.1371\/journal.ppat.1014555","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:39:33Z","timestamp":1790012373000},"page":"e1014555","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phosphorylated HPV\u201116 E7 disrupts planar cell polarity in cervical cancer cells through vangl1 dysregulation"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5123-8962","authenticated-orcid":true,"given":"Ifeoluwa D.","family":"Gbala","sequence":"first","affiliation":[{"name":"Tumour Virology, International Centre for Genetic Engineering and Biotechnology","place":["Trieste, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Om","family":"Basukala","sequence":"additional","affiliation":[{"name":"Tumour Virology, International Centre for Genetic Engineering and Biotechnology","place":["Trieste, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amira Zine","family":"El Abidine","sequence":"additional","affiliation":[{"name":"Tumour Virology, International Centre for Genetic Engineering and Biotechnology","place":["Trieste, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Myers","sequence":"additional","affiliation":[{"name":"Protein Networks, International Centre for Genetic Engineering and Biotechnology","place":["Trieste, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Bertolio","sequence":"additional","affiliation":[{"name":"Cancer Cell Signalling, International Centre for Genetic Engineering and Biotechnology","place":["Trieste, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giannino","family":"Del Sal","sequence":"additional","affiliation":[{"name":"Cancer Cell Signalling, International Centre for Genetic Engineering and Biotechnology","place":["Trieste, Italy"]},{"name":"University of Trieste","place":["Trieste, Italy"],"department":["Department of Life Science"]},{"name":"IFOM ETS, the AIRC Institute of Molecular Oncology","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Banks","sequence":"additional","affiliation":[{"name":"Tumour Virology, International Centre for Genetic Engineering and Biotechnology","place":["Trieste, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"ppat.1014555.ref001","unstructured":"World Health Organization. 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