Pregnancy-associated plasma protein a in cancer: expression, oncogenic functions and regulation

Pregnancy-associated plasma protein A (PAPPA) is a protease that plays important roles in pregnancy, but interestingly acts as an oncogene outside of pregnancy. This review summarizes the oncogenic roles of PAPPA, including its expression levels in multiple malignancies, regulatory and signaling interactions, and pro-tumor functions, which include promoting tumor cell proliferation, invasion, migration and metastasis. These PAPPA activities are linked to IGFBP-4 proteolysis, increased IFG bioavailability, and activation of the NF-kappa B, PI3K/AKT and ERK signaling pathways. Therefore, PAPPA could be used as a biomarker for monitoring cancer development and progression as well as a potential therapeutic target.