Miniatura

Fitxers

12474_4915081_13238_2019_article_630_mutationsinforegut.pdf (1.7 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2019-04-30

Llicència de publicació

cc by (c) Hishida et al., 2019
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/146620

Mutations in foregut SOX2+ cells induce efficient proliferation via CXCR2 pathway

Títol de la revista

Autors

ISSN de la revista

Títol del volum

Resum

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 KrasG12D 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 KrasG12D 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.

Descripció

Matèries

Tumors, Errors congènits del metabolisme

Matèries (anglès)

Inborn errors of metabolism

Citació

Col·leccions

Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

HISHIDA, Tomoaki, VAZQUEZ FERRER, Eric, HISHIDA NOZAKI, Yuriko, SANCHO-MARTINEZ, Ignacio, TAKAHASHI, Yuta, HATANAKA, Fumiyuki, WU, Jun, OCAMPO, Alejandro, REDDY, Pradeep, WU, Min-zu, GERKEN, Laurie, SHAW, Reuben j., RODRIGUEZ ESTEBAN, Concepción, BENNER, Christopher, NAKAGAWA, Hiroshi, GUILLEN GARCIA, Pedro, NUÑEZ DELICADO, Estrella, CASTELLS GARANGOU, Antoni, CAMPISTOL PLANA, Josep m., LIU, Guang-hui, IZPISÚA BELMONTE, Juan carlos. Mutations in foregut SOX2+ cells induce efficient proliferation via CXCR2 pathway. _Protein & Cell_. 2019. Vol. 10, núm. 7, pàgs. 485-495. [consulta: 3 de desembre de 2025]. ISSN: 1674-8018. [Disponible a: https://hdl.handle.net/2445/146620]

Exportar metadades

JSON - METS

Compartir registre