Impact of suppression of tumorigenicity 14 (ST14)/serine protease 14 (Prss14) expression analysis on the prognosis and management of estrogen receptor negative breast cancer.

To elucidate the role of a type II transmembrane serine protease, ST14/Prss14, during breast cancer progression, we utilized publically accessible databases including TCGA, GEO, NCI-60, and CCLE. Survival of breast cancer patients with high ST14/Prss14 expression is significantly poor in estrogen receptor (ER) negative populations regardless of the ratios of ST14/Prss14 to its inhibitors, SPINT1 or SPINT2. In a clustering of 1085 selected EMT signature genes, ST14/Prss14 is located in the same cluster with CDH3, and closer to post-EMT markers, CDH2, VIM, and FN1 than to the pre-EMT marker, CDH1. Coexpression analyses of known ST14/Prss14 substrates and transcription factors revealed context dependent action. In cell lines, paradoxically, ST14/Prss14 expression is higher in the ER positive group and located closer to CDH1 in clustering. This apparent contradiction is not likely due to ST14/Prss14 expression in a cancer microenvironment, nor due to negative regulation by ER. Genes consistently coexpressed with ST14/Prss14 include transcription factors, ELF5, GRHL1, VGLL1, suggesting currently unknown mechanisms for regulation. Here, we report that ST14/Prss14 is an emerging therapeutic target for breast cancer where HER2 is not applicable. In addition we suggest that careful conclusions should be drawn not exclusively from the cell line studies for target development.