RT Journal Article
T1 Mutation of SPINOPHILIN (PPP1R9B) found in human tumors promotes the tumorigenic and stemness properties of cells
A1 Verdugo-Sivianes, Eva M.
A1 Rojas, Ana M.
A1 Muñoz-Galván, Sandra
A1 Otero-Albiol, Daniel
A1 Carnero, Amancio
K1 SPINOPHILIN
K1 PP1
K1 Cancer stem cell
K1 Tumorigenesis
K1 Stem cell phenotype
K1 pRB
K1 Pocket proteins
K1 Retinoblastoma protein
K1 Breast cancer
K1 Cell lines
K1 Cell cycle
K1 Dephosphorylation
K1 Proteína fosfatasa 1
K1 Células madre neoplásicas
K1 Carcinogénesis
K1 Proteína 1 de unión a retinoblastoma
K1 Proteína de retinoblastoma
K1 Neoplasias de la mama
K1 Línea celular
AB Rationale: SPINOPHILIN (SPN, PPP1R9B) is an important tumor suppressor involved in the progression and malignancy of different tumors depending on its association with protein phosphatase 1 (PP1) and the ability of the PP1-SPN holoenzyme to dephosphorylate retinoblastoma (pRB). Methods: We performed a mutational analysis of SPN in human tumors, focusing on the region of interaction with PP1 and pRB. We explored the effect of the SPN-A566V mutation in an immortalized non-tumorigenic cell line of epithelial breast tissue, MCF10A, and in two different p53-mutated breast cancer cells lines, T47D and MDA-MB-468. Results: We characterized an oncogenic mutation of SPN found in human tumor samples, SPN-A566V, that affects both the SPN-PP1 interaction and its phosphatase activity. The SPN-A566V mutation does not affect the interaction of the PP1-SPN holoenzyme with pocket proteins pRB, p107 and p130, but it affects its ability to dephosphorylate them during G0/G1 and G1, indicating that the PP1-SPN holoenzyme regulates cell cycle progression. SPN-A566V also promoted stemness, establishing a connection between the cell cycle and stem cell biology via pocket proteins and PP1-SPN regulation. However, only cells with both SPN-A566V and mutant p53 have increased tumorigenic and stemness properties. Conclusions: SPN-A566V, or other equivalent mutations, could be late events that promote tumor progression by increasing the CSC pool and, eventually, the malignant behavior of the tumor.
PB Ivyspring International Publisher
YR 2021
FD 2021-01-19
LK http://hdl.handle.net/10668/4366
UL http://hdl.handle.net/10668/4366
LA en
NO Verdugo-Sivianes EM, Rojas AM, Muñoz-Galván S, Otero-Albiol D, Carnero A. Mutation of SPINOPHILIN (PPP1R9B) found in human tumors promotes the tumorigenic and stemness properties of cells. Theranostics. 2021 Jan 19;11(7):3452-3471.
DS RISalud
RD Apr 7, 2025