YAP-driven malignant reprogramming of oral epithelial stem cells at single cell resolution
Abstract Tumor initiation represents the first step in tumorigenesis during which normal progenitor cells undergo cell fate transition to cancer. Capturing this process as it occurs in vivo, however, remains elusive. Here we employ spatiotemporally controlled oncogene activation and tumor suppressor...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55660-6 |
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| author | Farhoud Faraji Sydney I. Ramirez Lauren M. Clubb Kuniaki Sato Valeria Burghi Thomas S. Hoang Adam Officer Paola Y. Anguiano Quiroz William M. G. Galloway Zbigniew Mikulski Kate Medetgul-Ernar Pauline Marangoni Kyle B. Jones Yuwei Cao Alfredo A. Molinolo Kenneth Kim Kanako Sakaguchi Joseph A. Califano Quinton Smith Alon Goren Ophir D. Klein Pablo Tamayo J. Silvio Gutkind |
| author_facet | Farhoud Faraji Sydney I. Ramirez Lauren M. Clubb Kuniaki Sato Valeria Burghi Thomas S. Hoang Adam Officer Paola Y. Anguiano Quiroz William M. G. Galloway Zbigniew Mikulski Kate Medetgul-Ernar Pauline Marangoni Kyle B. Jones Yuwei Cao Alfredo A. Molinolo Kenneth Kim Kanako Sakaguchi Joseph A. Califano Quinton Smith Alon Goren Ophir D. Klein Pablo Tamayo J. Silvio Gutkind |
| author_sort | Farhoud Faraji |
| collection | DOAJ |
| description | Abstract Tumor initiation represents the first step in tumorigenesis during which normal progenitor cells undergo cell fate transition to cancer. Capturing this process as it occurs in vivo, however, remains elusive. Here we employ spatiotemporally controlled oncogene activation and tumor suppressor inhibition together with multiomics to unveil the processes underlying oral epithelial progenitor cell reprogramming into tumor initiating cells at single cell resolution. Tumor initiating cells displayed a distinct stem-like state, defined by aberrant proliferative, hypoxic, squamous differentiation, and partial epithelial to mesenchymal invasive gene programs. YAP-mediated tumor initiating cell programs included activation of oncogenic transcriptional networks and mTOR signaling, and recruitment of myeloid cells to the invasive front contributing to tumor infiltration. Tumor initiating cell transcriptional programs are conserved in human head and neck cancer and associated with poor patient survival. These findings illuminate processes underlying cancer initiation at single cell resolution, and identify candidate targets for early cancer detection and prevention. |
| format | Article |
| id | doaj-art-e5971d932e7d400298d4ef57b0c8c908 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e5971d932e7d400298d4ef57b0c8c9082025-01-12T12:31:09ZengNature PortfolioNature Communications2041-17232025-01-0116112010.1038/s41467-024-55660-6YAP-driven malignant reprogramming of oral epithelial stem cells at single cell resolutionFarhoud Faraji0Sydney I. Ramirez1Lauren M. Clubb2Kuniaki Sato3Valeria Burghi4Thomas S. Hoang5Adam Officer6Paola Y. Anguiano Quiroz7William M. G. Galloway8Zbigniew Mikulski9Kate Medetgul-Ernar10Pauline Marangoni11Kyle B. Jones12Yuwei Cao13Alfredo A. Molinolo14Kenneth Kim15Kanako Sakaguchi16Joseph A. Califano17Quinton Smith18Alon Goren19Ophir D. Klein20Pablo Tamayo21J. Silvio Gutkind22Department of Otolaryngology-Head and Neck Surgery, University of California San Diego HealthDivision of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego HealthUniversity of California San Diego, Biomedical Sciences Graduate ProgramGleiberman Head and Neck Cancer Center, Moores Cancer Center, University of California San Diego HealthDepartment of Pharmacology, University of California San Diego, School of MedicineUniversity of California San Diego, Biomedical Sciences Graduate ProgramUniversity of California San Diego, Bioinformatics and Systems Biology Graduate ProgramGleiberman Head and Neck Cancer Center, Moores Cancer Center, University of California San Diego HealthDepartment of Chemical and Biomolecular Engineering, University of California IrvineLa Jolla Institute for ImmunologyGleiberman Head and Neck Cancer Center, Moores Cancer Center, University of California San Diego HealthDepartment of Orofacial Sciences and Program in Craniofacial Biology, University of California San FranciscoDepartment of Orofacial Sciences and Program in Craniofacial Biology, University of California San FranciscoUniversity of California San Diego, Biomedical Sciences Graduate ProgramGleiberman Head and Neck Cancer Center, Moores Cancer Center, University of California San Diego HealthLa Jolla Institute for ImmunologyIDEXX Laboratories KKDepartment of Otolaryngology-Head and Neck Surgery, University of California San Diego HealthDepartment of Chemical and Biomolecular Engineering, University of California IrvineDivision of Medical Genetics, Department of Medicine, University of California San DiegoDepartment of Orofacial Sciences and Program in Craniofacial Biology, University of California San FranciscoGleiberman Head and Neck Cancer Center, Moores Cancer Center, University of California San Diego HealthGleiberman Head and Neck Cancer Center, Moores Cancer Center, University of California San Diego HealthAbstract Tumor initiation represents the first step in tumorigenesis during which normal progenitor cells undergo cell fate transition to cancer. Capturing this process as it occurs in vivo, however, remains elusive. Here we employ spatiotemporally controlled oncogene activation and tumor suppressor inhibition together with multiomics to unveil the processes underlying oral epithelial progenitor cell reprogramming into tumor initiating cells at single cell resolution. Tumor initiating cells displayed a distinct stem-like state, defined by aberrant proliferative, hypoxic, squamous differentiation, and partial epithelial to mesenchymal invasive gene programs. YAP-mediated tumor initiating cell programs included activation of oncogenic transcriptional networks and mTOR signaling, and recruitment of myeloid cells to the invasive front contributing to tumor infiltration. Tumor initiating cell transcriptional programs are conserved in human head and neck cancer and associated with poor patient survival. These findings illuminate processes underlying cancer initiation at single cell resolution, and identify candidate targets for early cancer detection and prevention.https://doi.org/10.1038/s41467-024-55660-6 |
| spellingShingle | Farhoud Faraji Sydney I. Ramirez Lauren M. Clubb Kuniaki Sato Valeria Burghi Thomas S. Hoang Adam Officer Paola Y. Anguiano Quiroz William M. G. Galloway Zbigniew Mikulski Kate Medetgul-Ernar Pauline Marangoni Kyle B. Jones Yuwei Cao Alfredo A. Molinolo Kenneth Kim Kanako Sakaguchi Joseph A. Califano Quinton Smith Alon Goren Ophir D. Klein Pablo Tamayo J. Silvio Gutkind YAP-driven malignant reprogramming of oral epithelial stem cells at single cell resolution Nature Communications |
| title | YAP-driven malignant reprogramming of oral epithelial stem cells at single cell resolution |
| title_full | YAP-driven malignant reprogramming of oral epithelial stem cells at single cell resolution |
| title_fullStr | YAP-driven malignant reprogramming of oral epithelial stem cells at single cell resolution |
| title_full_unstemmed | YAP-driven malignant reprogramming of oral epithelial stem cells at single cell resolution |
| title_short | YAP-driven malignant reprogramming of oral epithelial stem cells at single cell resolution |
| title_sort | yap driven malignant reprogramming of oral epithelial stem cells at single cell resolution |
| url | https://doi.org/10.1038/s41467-024-55660-6 |
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