The Controversial Aspects on the Expression Profiles and the Action of ST14 (Epithin, PRSS14, Matriptase) during Epithelial-Mesenchymal Transition and Cancer Progression

초록

Epithin/PRSS14 (also known as ST14 and matriptase) is an epithelial-derived, type II transmembrane serine protease that is widely overexpressed in epithelial cancer types. Although its name “Suppressive of tumor 14” was originated from the fact that its expression is downregulated in certain sets of tumors, its expression profiles have been widely associated with the progression of tumors. Currently, many data derived from expression array analysis of cancer cell and human cancer types suggested ST14 is one of the top candidate genes for the EMT/metastasis signature. We have shown, using gene specific knock down cells, that it plays critical functions in angiogenesis, epithelial mesenchymal transition, transendothelial cell migration in culture, and in metastasis of breast cancers in immunocompetent syngenic mice. According to human cancer patients data from commercial (Oncomine) database, its message expression was up-regulated only up to the point of certain stages of cancers, suggesting its expression is modulated down there after. Using various publically available expression data sets including TCGA and GES, we examined the ST14 expression profiles of several selected types and stages of epithelial cancers (breast, ovarian, and colon cancers) by comparing to other well-known 70 EMT signature genes. Cluster analysis showed that ST14 was associated with the genes of post-EMT signature genes. These results raise a question how to reconcile the apparent controversies of expression profiling and how epithin/PRSS14 functions in EMT and during metastasis. Therefore, the interpretation solely based on array data of relative expression profiles, which are not quantitative values can be misleading. We will propose putative mechanisms that might explain the expression patterns and verified functions during the poster session. More quantitative data of absolute numbers (such as from RNA seq) in the expression profiling as well as functional verification such as protein