학술논문
KRAS mutant rectal cancer cells interact with surrounding fibroblasts to deplete the extracellular matrix
Document Type
article
Author
Jin K. Kim; Michael R. Marco; Seo‐Hyun Choi; Xuan Qu; Chin‐Tung Chen; Moshe Elkabets; Lauren Fairchild; Oliver Chow; Francisco M. Barriga; Lukas E. Dow; Kevin O’Rourke; Bryan Szeglin; Dmitry Yarilin; Sho Fujisawa; Katia Manova‐Todorova; Philip B. Paty; Jinru Shia; Christina Leslie; J. Joshua Smith; Scott Lowe; Raphael Pelossof; Francisco Sanchez‐Vega; Julio Garcia‐Aguilar
Source
Molecular Oncology, Vol 15, Iss 10, Pp 2766-2781 (2021)
Subject
Language
English
ISSN
1878-0261
1574-7891
1574-7891
Abstract
Somatic mutations in the KRAS oncogene are associated with poor outcomes in locally advanced rectal cancer but the underlying biologic mechanisms are not fully understood. We profiled mRNA in 76 locally advanced rectal adenocarcinomas from patients that were enrolled in a prospective clinical trial and investigated differences in gene expression between KRAS mutant (KRAS‐mt) and KRAS‐wild‐type (KRAS‐wt) patients. We found that KRAS‐mt tumors display lower expression of genes related to the tumor stroma and remodeling of the extracellular matrix. We validated our findings using samples from The Cancer Genome Atlas (TCGA) and also by performing immunohistochemistry (IHC) and immunofluorescence (IF) in orthogonal cohorts. Using in vitro and in vivo models, we show that oncogenic KRAS signaling within the epithelial cancer cells modulates the activity of the surrounding fibroblasts in the tumor microenvironment.