| First Author | Guo W | Year | 2006 |
| Journal | Cell | Volume | 126 |
| Issue | 3 | Pages | 489-502 |
| PubMed ID | 16901783 | Mgi Jnum | J:115020 |
| Mgi Id | MGI:3690559 | Doi | 10.1016/j.cell.2006.05.047 |
| Citation | Guo W, et al. (2006) Beta 4 integrin amplifies ErbB2 signaling to promote mammary tumorigenesis. Cell 126(3):489-502 |
| abstractText | Amplification of the ErbB2 locus, which encodes a receptor tyrosine kinase, is common in aggressive breast tumors and correlates with poor prognosis. The mechanisms underlying ErbB2-mediated breast carcinoma progression remain incompletely defined. To examine the role of the signaling and cell-adhesion receptor beta 4 integrin during ErbB2-mediated tumorigenesis, we introduced a targeted deletion of the beta 4 signaling domain into a mouse model of ErbB2-induced mammary carcinoma. Loss of beta 4 signaling suppresses mammary tumor onset and invasive growth. Ex vivo studies indicate that beta 4 forms a complex with ErbB2 and enhances activation of the transcription factors STAT3 and c-Jun. STAT3 contributes to disruption of epithelial adhesion and polarity, while c-Jun is required for hyperproliferation. Finally, deletion of the beta 4 signaling domain enhances the efficacy of ErbB2-targeted therapy. These results indicate that beta 4 integrin promotes tumor progression by amplifying ErbB2 signaling and identify beta 4 as a potential target for molecular therapy of breast cancer. |
