SPINOPHILIN: A multiplayer tumor suppressor

SPINOPHILIN (SPN, PPP1R9B or NEURABIN-2) is a multifunctional protein that regu-lates 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 re-ported 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 pro-gression by increasing the CSC pool and, eventually, the malignant behavior of the tumor. (c) 2022 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).

Automated summary

SPINOPHILIN (SPN) is a multifunctional protein involved in regulating protein-protein interactions and the dephosphorylation of pRB, which plays a role in cell cycle progression. SPN has been identified as a tumor suppressor gene, and mutations in the SPN protein have been associated with human tumors. Furthermore, an oncogenic mutation, A566V, has been shown to promote tumorigenesis by increasing the CSC pool in breast tumors. Loss or mutation of SPN may contribute to tumor progression by enhancing CSC populations and malignant behavior.