Academic Journal
Mutations in foregut SOX2+ cells induce efficient proliferation via CXCR2 pathway
| العنوان: | Mutations in foregut SOX2+ cells induce efficient proliferation via CXCR2 pathway |
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| المؤلفون: | Tomoaki Hishida, Eric Vazquez-Ferrer, Yuriko Hishida-Nozaki, Ignacio Sancho-Martinez, Yuta Takahashi, Fumiyuki Hatanaka, Jun Wu, Alejandro Ocampo, Pradeep Reddy, Min-Zu Wu, Laurie Gerken, Reuben J. Shaw, Concepcion Rodriguez Esteban, Christopher Benner, Hiroshi Nakagawa, Pedro Guillen Garcia, Estrella Nuñez Delicado, Antoni Castells, Josep M. Campistol, Guang-Hui Liu, Juan Carlos Izpisua Belmonte |
| المصدر: | Protein & Cell, Vol 10, Iss 7, Pp 485-495 (2019) |
| بيانات النشر: | Oxford University Press |
| سنة النشر: | 2019 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Sox2, tumor, CXCR2, stratified epithelia, Cytology, QH573-671, Animal biochemistry, QP501-801 |
| الوصف: | Identification of the precise molecular pathways involved in oncogene-induced transformation may help us gain a better understanding of tumor initiation and promotion. Here, we demonstrate that SOX2+ foregut epithelial cells are prone to oncogenic transformation upon mutagenic insults, such as Kras G12D and p53 deletion. GFP-based lineage-tracing experiments indicate that SOX2+ cells are the cells-of-origin of esophagus and stomach hyperplasia. Our observations indicate distinct roles for oncogenic KRAS mutation and P53 deletion. p53 homozygous deletion is required for the acquisition of an invasive potential, and Kras G12D expression, but not p53 deletion, suffices for tumor formation. Global gene expression analysis reveals secreting factors upregulated in the hyperplasia induced by oncogenic KRAS and highlights a crucial role for the CXCR2 pathway in driving hyperplasia. Collectively, the array of genetic models presented here demonstrate that stratified epithelial cells are susceptible to oncogenic insults, which may lead to a better understanding of tumor initiation and aid in the design of new cancer therapeutics. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1674-800X 1674-8018 |
| Relation: | http://link.springer.com/article/10.1007/s13238-019-0630-3; https://doaj.org/toc/1674-800X; https://doaj.org/toc/1674-8018; https://doaj.org/article/650bfe1468004174b4f346e6bcc81813 |
| DOI: | 10.1007/s13238-019-0630-3 |
| الاتاحة: | https://doi.org/10.1007/s13238-019-0630-3 https://doaj.org/article/650bfe1468004174b4f346e6bcc81813 |
| رقم الانضمام: | edsbas.A2007D70 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 1674800X 16748018 |
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| DOI: | 10.1007/s13238-019-0630-3 |