Academic Journal
PRKCI-ECT2 copy number gain promotes developmental reprogramming and metastatic competence in lung adenocarcinoma.
| Τίτλος: | PRKCI-ECT2 copy number gain promotes developmental reprogramming and metastatic competence in lung adenocarcinoma. |
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| Συγγραφείς: | Nguyen DT; Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, FL, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN, USA., Meneses KM; Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, FL, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA., Zhang C; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN, USA., Prieto LI; Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA; Department of Pediatrics, Mayo Clinic College of Medicine, Rochester, MN, USA., Weems C; Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, FL, USA., Jamieson L; Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, FL, USA., Li H; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN, USA., Baker DJ; Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN, USA; Department of Pediatrics, Mayo Clinic College of Medicine, Rochester, MN, USA; Paul F. Glenn Center for Biology of Aging Research, Mayo Clinic College of Medicine, Rochester, MN, USA; Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine, Rochester, MN, USA., Khoor A; Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Jacksonville, FL, USA., Murray NR; Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, FL, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN, USA., Justilien V; Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, FL, USA., Fields AP; Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, FL, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN, USA. Electronic address: fields.alan@mayo.edu. |
| Πηγή: | Cell reports [Cell Rep] 2026 Jul 28; Vol. 45 (7), pp. 117697. Date of Electronic Publication: 2026 Jul 18. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Cambridge, MA] : Cell Press, c 2012- |
| Ιατρικοί όροι (MeSH): | Protein Kinase C*/metabolism , Protein Kinase C*/genetics , Lung Neoplasms*/genetics , Lung Neoplasms*/pathology , Lung Neoplasms*/metabolism , Adenocarcinoma of Lung*/genetics , Adenocarcinoma of Lung*/pathology , Proto-Oncogene Proteins*/genetics , Proto-Oncogene Proteins*/metabolism , Cellular Reprogramming*/genetics , DNA Copy Number Variations*/genetics, Isoenzymes/metabolism ; Isoenzymes/genetics ; SOX9 Transcription Factor/metabolism ; Animals ; Protein Kinase C-lambda ; Humans ; Mice ; Neoplasm Metastasis ; Signal Transduction |
| Περίληψη: | Lung adenocarcinoma (LUAD) shows extensive lineage plasticity and early metastatic dissemination, but the oncogenic events that actively drive these processes remain poorly defined. Here, we identify coordinated PRKCI and ECT2 copy number gain, present in approximately 30% of human LUADs, as a driver of developmental reprogramming and metastasis. Using a genetically engineered mouse model that recapitulates PRKCI-ECT2 gain in Kras/Trp53-driven LUAD, we show that elevated PKCι-ECT2 signaling rewires tumor trajectory in a cell-of-origin-dependent manner. Alveolar type II cell-derived tumors dedifferentiate into a distal SOX9high progenitor-like state associated with aggressive growth and liver metastasis, whereas club cell-derived tumors transition into a foregut SOX2high progenitor-like state that supports lineage infidelity and histological transformation. Human LUAD analyses support these progenitor programs as clinically relevant features of PRKCI-ECT2 gain. (Copyright © 2026 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of interests The authors declare no competing interests. |
| Contributed Indexing: | Keywords: CP: Cancer; CP: Developmental biology; ECT2; PRKCI; SOX2; SOX9; copy number gain; developmental reprogramming; lineage plasticity; lung adenocarcinoma; metastasis; single-cell RNA sequencing |
| Substance Nomenclature: | EC 2.7.11.13 (Protein Kinase C-lambda) EC 2.7.11.13 (Protein Kinase C) 0 (Proto-Oncogene Proteins) 0 (Isoenzymes) 0 (ECT2 protein, human) 0 (SOX9 Transcription Factor) |
| Entry Date(s): | Date Created: 20260718 Date Completed: 20260730 Latest Revision: 20260730 |
| Update Code: | 20260730 |
| DOI: | 10.1016/j.celrep.2026.117697 |
| PMID: | 42470637 |
| Βάση Δεδομένων: | MEDLINE |
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