K-Ras and B-Raf oncogenes inhibit colon epithelial polarity establishment through up-regulation of c-myc Journal Article
| Authors: | Magudia, K.; Lahoz, A.; Hall, A. |
| Article Title: | K-Ras and B-Raf oncogenes inhibit colon epithelial polarity establishment through up-regulation of c-myc |
| Abstract: | KRAS, BRAF, and PI3KCA are the most frequently mutated oncogenes in human colon cancer. To explore their effects on morphogenesis, we used the colon cancer-derived cell line Caco-2. When seeded in extracellular matrix, individual cells proliferate and generate hollow, polarized cysts. The expression of on-cogenic phosphatidylinositol 3-kinase (PI3KCA H1047R) in Caco-2 has no effect, but K-Ras V12 or B-Raf V600E disrupts polarity and tight junctions and promotes hyper-proliferation, resulting in large, filled structures. Inhibition of mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase blocks the disruption of morphology, as well as the increased levels of c-myc protein induced by K-Ras V12 and B-Raf V600E. Apical polarity is already established after the first cell division (two-cell stage) in Caco-2 three-dimensional cultures. This is disrupted by expression of K-Ras V12 or B-Raf V600E but can be res-cued by ribonucleic acid interference-mediated depletion of c-myc. We conclude that ERK-mediated up-regulation of c-myc by K-Ras or B-Raf oncogenes disrupts the estab-lishment of apical/basolateral polarity in colon epithelial cells independently of its effect on proliferation. © 2012 Magudia et al. |
| Journal Title: | Journal of Cell Biology |
| Volume: | 198 |
| Issue: | 2 |
| ISSN: | 0021-9525 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2012-07-23 |
| Start Page: | 185 |
| End Page: | 194 |
| Language: | English |
| DOI: | 10.1083/jcb.201202108 |
| PROVIDER: | scopus |
| PMCID: | PMC3410422 |
| PUBMED: | 22826122 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 4 September 2012" - "CODEN: JCLBA" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work