Triple-negative breast cancer is difficult to treat because of the lack of 
rationale-based therapies. There are no established markers and targets that can 
be used for stratification of patients and targeted therapy. Here we report the 
identification of novel molecular features, which appear to augment metastasis 
of triple negative breast tumors. We found that triple-negative breast tumors 
can be segregated into 2 phenotypes based on their genome-wide protein abundance 
profiles. The first is characterized by high expression of Stat1, Mx1, and CD74. 
Seven out of 9 tumors from this group had invaded at least 2 lymph nodes while 
only 1 out of 10 tumors in group 2 was lymph node positive. In vitro experiments 
showed that the interferon-induced increase in Stat1 abundance correlates with 
increased migration and invasion in cultured cells. When CD74 was overexpressed, 
it increased cell adhesion on matrigel. This effect was accompanied with a 
marked increase in the membrane expression of beta-catenin, MUC18, plexins, 
integrins, and other proteins involved in cell adhesion and cancer metastasis. 
Taken together, our results show that Stat1/CD74 positive triple-negative tumors 
are more aggressive and suggest an approach for development of better 
diagnostics and more targeted therapies for triple negative breast cancer. This 
article is part of a Special Issue entitled: Proteomics: The clinical link.