Open AccessKRAS mutant rectal cancer cells interact with surrounding fibroblasts to deplete the extracellular matrix
Author(s) -
Kim Jin K.,
Marco Michael R.,
Choi SeoHyun,
Qu Xuan,
Chen ChinTung,
Elkabets Moshe,
Fairchild Lauren,
Chow Oliver,
Barriga Francisco M.,
Dow Lukas E.,
O’Rourke Kevin,
Szeglin Bryan,
Yarilin Dmitry,
Fujisawa Sho,
ManovaTodorova Katia,
Paty Philip B.,
Shia Jinru,
Leslie Christina,
Smith J. Joshua,
Lowe Scott,
Pelossof Raphael,
SanchezVega Francisco,
GarciaAguilar Julio
Publication year - 2021
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12960
Subject(s) - kras , cancer research , colorectal cancer , immunohistochemistry , stroma , oncogene , biology , extracellular matrix , cancer , stromal cell , pathology , medicine , microbiology and biotechnology , genetics , cell cycle
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.