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Protein kinase C-eta (PKC\u03b7), an antiapoptotic kinase of the novel PKC subfamily, is associated with poor prognosis in breast cancer patients. Analysis of TNBC tumors revealed that\n                    <jats:italic>PRKCH<\/jats:italic>\n                    (PKC\u03b7) expression is linked to an epithelial\u2012mesenchymal transition (EMT) signature, which is indicative of a metastatic phenotype. Using genetic ablation studies, we showed that PKC\u03b7 promotes metastasis by enhancing EMT and stemness. Notably, compared with those in PKC\u03b7-intact tumors, orthotopic xenografts of PKC\u03b7-knockout cells in NSG mice resulted in reduced tumor growth and metastasis. Mechanistically, PKC\u03b7 functions as a negative regulator of the Hippo pathway by activating YAP. PKC\u03b7 phosphorylates YAP at Ser128, leading to its stabilization and nuclear translocation, which promotes metastasis. We also demonstrated that PKC\u03b7 negatively regulates AKT, thereby further sustaining the downregulation of the Hippo pathway. Finally, we show that an evolutionarily conserved peptide encoded by an upstream open reading frame (uORF) preceding the PKC\u03b7 coding sequence functions as a PKC\u03b7 degrader, activating the Hippo pathway and promoting YAP degradation. Together, our findings reveal a PKC\u03b7-driven signaling axis that regulates the Hippo\u2013YAP pathway in TNBC metastasis, highlighting the potential therapeutic vulnerability of this aggressive disease.\n                  <\/jats:p>","DOI":"10.1038\/s41392-026-02572-0","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:02:18Z","timestamp":1771286538000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["PKC-eta promotes breast cancer metastasis by regulating the Hippo\u2013YAP signaling pathway"],"prefix":"10.1038","volume":"11","author":[{"given":"Vijayasteltar B.","family":"Liju","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0665-9370","authenticated-orcid":false,"given":"Kamran","family":"Waidha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amitha","family":"Muraleedharan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divya Ram","family":"Jayaram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hodaya","family":"Haimov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3778-8757","authenticated-orcid":false,"given":"Sankar","family":"Jagadeeshan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh Babu","family":"Manikandan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raghda Abu","family":"Shareb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livingstone","family":"Nurukurti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menachem","family":"Sklarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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