| First Author | Worzfeld T | Year | 2012 |
| Journal | J Clin Invest | Volume | 122 |
| Issue | 4 | Pages | 1296-305 |
| PubMed ID | 22378040 | Mgi Jnum | J:184562 |
| Mgi Id | MGI:5424318 | Doi | 10.1172/JCI60568 |
| Citation | Worzfeld T, et al. (2012) ErbB-2 signals through Plexin-B1 to promote breast cancer metastasis. J Clin Invest 122(4):1296-305 |
| abstractText | Diagnosis of metastatic breast cancer is associated with a very poor prognosis. New therapeutic targets are urgently needed, but their development is hampered by a lack of understanding of the mechanisms leading to tumor metastasis. Exemplifying this is the fact that the approximately 30% of all breast cancers overexpressing the receptor tyrosine kinase ErbB-2 are characterized by high metastatic potential and poor prognosis, but the signaling events downstream of ErbB-2 that drive cancer cell invasion and metastasis remain incompletely understood. Here we show that overexpression of ErbB-2 in human breast cancer cell lines leads to phosphorylation and activation of the semaphorin receptor Plexin-B1. This was required for ErbB-2-dependent activation of the pro-metastatic small GTPases RhoA and RhoC and promoted invasive behavior of human breast cancer cells. In a mouse model of ErbB-2-overexpressing breast cancer, ablation of the gene encoding Plexin-B1 strongly reduced the occurrence of metastases. Moreover, in human patients with ErbB-2-overexpressing breast cancer, low levels of Plexin-B1 expression correlated with good prognosis. Our data suggest that Plexin-B1 represents a new candidate therapeutic target for treating patients with ErbB-2-positive breast cancer. |
