KRAS mutant rectal cancer cells interact with surrounding fibroblasts to deplete the extracellular matrix Journal Article
| Authors: | Kim, J. K.; Marco, M. R.; Choi, S. H.; Qu, X.; Chen, C. T.; Elkabets, M.; Fairchild, L.; Chow, O.; Barriga, F. M.; Dow, L. E.; O'Rourke, K.; Szeglin, B.; Yarilin, D.; Fujisawa, S.; Manova-Todorova, K.; Paty, P. B.; Shia, J.; Leslie, C.; Smith, J. J.; Lowe, S.; Pelossof, R.; Sanchez-Vega, F.; Garcia-Aguilar, J. |
| Article Title: | KRAS mutant rectal cancer cells interact with surrounding fibroblasts to deplete the extracellular matrix |
| 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. © 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies |
| Keywords: | extracellular matrix; kras; rectal cancer; tumor response; tumor stroma; cancer-associated fibroblast |
| Journal Title: | Molecular Oncology |
| Volume: | 15 |
| Issue: | 10 |
| ISSN: | 1878-0261 |
| Publisher: | FEBS Press |
| Date Published: | 2021-10-01 |
| Start Page: | 2766 |
| End Page: | 2781 |
| Language: | English |
| PMCID: | PMC8486594 |
| DOI: | 10.1002/1878-0261.12960 |
| PROVIDER: | scopus |
| PUBMED: | 33817986 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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