Year: 2019
Type: article
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.
Source: Protein & Cell
Authors: 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
Institutions: Salk Institute for Biological Studies, Universidad Católica de Murcia, Howard Hughes Medical Institute, Abramson Cancer Center, University of Pennsylvania, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, Capital Medical University, Chinese Academy of Sciences, Xuan Wu Hospital of the Capital Medical University, Institute of Biophysics, University of Chinese Academy of Sciences, Beijing Institute for Brain Disorders
Language: English
Topic: Cancer Cells and Metastasis
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid:
Funders: Pioneer Fund, Leona M. and Harry B. Helmsley Charitable Trust, Moxie Foundation, National Natural Science Foundation of China, Chinese Academy of Sciences, Beijing Municipal Science and Technology Commission, National Institutes of Health, National Key Research and Development Program of China, National Cancer Institute
OpenAlex ID: W2942590745