SPINOPHILIN (SPN, PPP1R9B or
NEURABIN-2) is a multifunctional
protein that regulates
protein-
protein interactions in different cell signaling pathways. SPN is also one of the regulatory subunits of
protein phosphatase 1 (PP1), implicated in the dephosphorylation of
retinoblastoma protein (pRB) during cell cycle. The SPN gene has been described as a
tumor suppressor in different human
tumor contexts, in which low levels of SPN are correlated with a higher grade and worse prognosis. In addition, mutations of the SPN
protein have been reported in human
tumors. Recently, an oncogenic mutation of SPN, A566V, was described, which affects both the SPN-PP1 interaction and the
phosphatase activity of the
holoenzyme, and promotes p53-dependent
tumorigenesis by increasing the cancer stem cell (CSC) pool in
breast tumors. Thus, the loss or mutation of SPN could be late events that promotes
tumor progression by increasing the CSC pool and, eventually, the malignant behavior of the
tumor.