Verdugo-Sivianes, Eva M.Rojas, Ana M.Muñoz-Galván, SandraOtero-Albiol, DanielCarnero, Amancio2022-11-212022-11-212021-01-19Verdugo-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.http://hdl.handle.net/10668/4366Rationale: 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/SPINOPHILINPP1Cancer stem cellTumorigenesisStem cell phenotypepRBPocket proteinsRetinoblastoma proteinBreast cancerCell linesCell cycleDephosphorylationProteína fosfatasa 1Células madre neoplásicasCarcinogénesisProteína 1 de unión a retinoblastomaProteína de retinoblastomaNeoplasias de la mamaLínea celularMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Breast NeoplasmsMedical Subject Headings::Diseases::Neoplasms::Neoplastic Processes::CarcinogenesisMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, TransformedMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, TumorMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Cycle::Cell Cycle Checkpoints::G1 Phase Cell Cycle CheckpointsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Gene Expression Regulation, NeoplasticMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Mutant Strains::Mice, NudeMedical Subject Headings::Chemicals and Drugs::Macromolecular Substances::Polymers::Biopolymers::Microfilament ProteinsMedical Subject Headings::Anatomy::Cells::Stem Cells::Neoplastic Stem CellsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nerve Tissue ProteinsMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::PhosphorylationMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Phosphoric Monoester Hydrolases::Phosphoprotein Phosphatases::Protein Phosphatase 1Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins::Tumor Suppressor Proteins::Retinoblastoma ProteinMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Signal TransductionMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins::Tumor Suppressor Proteins::Tumor Suppressor Protein p53Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Evaluation Studies as Topic::Drug Evaluation, Preclinical::Drug Screening Assays, Antitumor::Xenograft Model Antitumor AssaysMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell LineMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell CycleMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::MutationMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::HoloenzymesMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Eye Neoplasms::Retinal Neoplasmsresearch article33537097open access10.7150/thno.535721838-7640PMC7847670