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Title: Mutations in foregut SOX2+ cells induce efficient proliferation via CXCR2 pathway
Author: 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
Keywords: Tumors
Errors congènits del metabolisme
Inborn errors of metabolism
Issue Date: 30-Apr-2019
Publisher: Springer Nature
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: Protein & Cell, 2019, vol. 10, num. 7, p. 485-495
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ISSN: 1674-8018
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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