Pleiotropic functions of EAPII/TTRAP/TDP2: cancer development, chemoresistance and beyond.

EAPII (also called TTRAP, TDP2), a protein identified a decade ago, has recently been shown to function as an oncogenic factor. This protein was also proven to be the first 5'- tyrosyl-DNA phosphodiesterase. EAPII has been demonstrated to have promiscuous protein associations, broad responsiveness to various extracellular signals, and pleiotropic functions in the development of human diseases including cancer and neurodegenerative disease. Emerging data suggest that EAPII is a multi-functional protein: EAPII repairs enzyme (topoisomerase)-mediated DNA damage by removing phosphotyrosine from DNA adducts; EAPII is involved in multiple signal transduction pathways such as TNF-TNFR, TGFβ and MAPK, and EAPII is responsive to immune defense, inflammatory response, virus infection and DNA toxins (chemo or radiation therapy). This review focuses on the current understanding of EAPII biology and its potential relations to many aspects of cancer development, including chromosome instability, tumorigenesis, tumor metastasis and chemoresistance, suggesting it as a potential target for intervention in cancer and other human diseases.