The Ras-related gene ERAS is involved in human and murine breast cancer

Scientific Reports
Cristian Suárez-CabreraManuel Navarro

Abstract

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 ...Continue Reading

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Citations

Dec 13, 2019·Nature Communications·Youli XiaCharles M Perou
Jul 9, 2020·Nature Reviews. Cancer·Julia WeberRoland Rad
Feb 23, 2020·Frontiers in Cell and Developmental Biology·Huajian TianQinghua Zhou
Feb 20, 2020·Military Medicine·Alakesh BeraMeera Srivastava
Dec 22, 2020·Frontiers in Cell and Developmental Biology·Jing-Li XuJiang-Jiang Qin

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Methods Mentioned

BETA
GTPases
Illumina sequencing
confocal microscopy
flow cytometry
xenograft
transgenic
GTPase
PCR
transfection
electrophoresis

Software Mentioned

Survival package
ImageLab
FlowJo
SPSS Statistics
NormFinder
geNorm
R
GSEA
Gene Set Enrichment Analysis ( GSEA )
ImageJ

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