Journal
SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-018-31326-4
Keywords
-
Categories
Funding
- ISCIII National Biobank Record [B.0000657]
- MD Anderson Foundation Biobank (ISCIII National Biobank Record) [B.0000745]
- Fondo Europeo de Desarrollo Regional (FEDER)
- Spanish Government from Instituto de Salud Carlos III (Ministerio de Economia y Competitividad) [PI16/00161, PI16/00134, PIE15/00076, PI17/00578, CB/16/00228, CB16/12/00295, RD12/0036/0009]
- Ministerio de Economia y Competitividad [SAF-2015-66015-R]
- Instituto de Salud Carlos III
Ask authors/readers for more resources
Although Ras genes are frequently mutated in human tumors, these mutations are uncommon in breast cancer. However, many breast tumors show evidences of Ras pathway activation. In this manuscript, we have analyzed and characterized mouse mammary tumors generated by random Sleeping Beauty transposon mutagenesis and identify ERAS -a member of the RAS family silenced in adult tissues-as a new gene involved in progression and malignancy of breast cancer. Forced expression of ERAS in human non-transformed mammary gland cells induces a process of epithelial-to-mesenchymal transition and an increase in stem cells markers; these changes are mediated by miR-200c downregulation. ERAS expression in human tumorigenic mammary cells leads to the generation of larger and less differentiated tumors in xenotransplant experiments. Immunohistochemical, RT-qPCR and bioinformatics analysis of human samples show that ERAS is aberrantly expressed in 8-10% of breast tumors and this expression is associated with distant metastasis and reduced metastasis-free survival. In summary, our results reveal that inappropriate activation of ERAS may be important in the development of a subset of breast tumors. These findings open the possibility of new specific treatments for this subset of ERAS-expressing tumors.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available