Enhanced MAF Oncogene Expression and Breast Cancer Bone Metastasis.

Background: There are currently no biomarkers for early breast cancer patient populations at risk of bone metastasis. Identification of mediators of bone metastasis could be of clinical interest.

Methods: A de novo unbiased screening approach based on selection of highly bone metastatic breast cancer cells in vivo was used to determine copy number aberrations (CNAs) associated with bone metastasis.

Identification of NOG as a specific breast cancer bone metastasis-supporting gene.

Metastasis requires numerous biological functions that jointly provide tumor cells from a primary site to seed and colonize a distant organ. Some of these activities are selected for in the primary site, whereas others are acquired at the metastatic niche. We provide molecular evidence showing that the BMP inhibitor, NOG, provides metastatic breast cancer cells with the ability to colonize the bone.

Tumor-stroma interactions a trademark for metastasis.

Aims: We aimed to unravel genes that are significantly associated with metastasis in order to identify functions that support disseminated disease.

Methods And Results: We identify genes associated with metastasis and verify its clinical correlations using publicly available primary tumor expression profile data sets. We used facilities in R and Bioconductor (GSEA).

HER2 silences tumor suppression in breast cancer cells by switching expression of C/EBPß isoforms.

Tumor progression requires ablation of suppressor functions mediated by transforming growth factor β (TGFβ) signaling and by oncogene-induced senescence (OIS), but how these functions are canceled in specific subtypes of breast cancer remains unknown. In this study, we show that HER2-overexpressing breast cancer cells avert TGFβ- and OIS-mediated tumor suppression by switching expression of 2 functionally distinct isoforms of the transcription factor C/EBPβ, which has been implicated previously in breast cancer development. HER2 signaling activates the translational regulatory factor CUGBP1, which favors the production of the transcriptionally inhibitory isoform LIP over that of the active isoform LAP.