ArticleOncogene2016
Loss of the tumor suppressor spinophilin (PPP1R9B) increases the cancer stem cell population in breast tumors.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Differential splicing of neuronal genes in a Trem2*R47H mouse model mimics alterations associated with Alzheimer's disease.BMC genomics · 2023Article
- OLA1 Phosphorylation: A Distress Signal from Damaged Endothelial Mitochondria?American journal of respiratory cell and molecular biology · 2023Article
- OLA1 Phosphorylation Governs the Mitochondrial Bioenergetic Function of Pulmonary Vascular Cells.American journal of respiratory cell and molecular biology · 2023Article
- Differences in genome, transcriptome, miRNAome, and methylome in synchronous and metachronous liver metastasis of colorectal cancer.Frontiers in oncology · 2023Article
- SPINOPHILIN: A multiplayer tumor suppressor.Genes & diseases · 2023Review
- Empty spiracles homeobox genes EMX1 and EMX2 regulate WNT pathway activation in sarcomagenesis.Journal of experimental & clinical cancer research : CR · 2021Article
- PP1, PKA and DARPP-32 in breast cancer: A retrospective assessment of protein and mRNA expression.Journal of cellular and molecular medicine · 2021Article
- Regulation of sarcomagenesis by the empty spiracles homeobox genes EMX1 and EMX2.Cell death & disease · 2021Article
- Role of the Holoenzyme PP1-SPN in the Dephosphorylation of the RB Family of Tumor Suppressors During Cell Cycle.Cancers · 2021Review
- Mutation of SPINOPHILIN (PPP1R9B) found in human tumors promotes the tumorigenic and stemness properties of cells.Theranostics · 2021Article
- Downregulation of MYPT1 increases tumor resistance in ovarian cancer by targeting the Hippo pathway and increasing the stemness.Molecular cancer · 2020Article
- The Scribble Complex PDZ Proteins in Immune Cell Polarities.Journal of immunology research · 2020Review
- Therapeutic Targeting of Signaling Pathways Related to Cancer Stemness.Frontiers in oncology · 2020Review
- Article
- Novel and Alternative Targets Against Breast Cancer Stemness to Combat Chemoresistance.Frontiers in oncology · 2019Review
- Dr. Jekyll and Mr. Hyde: MAP17's up-regulation, a crosspoint in cancer and inflammatory diseases.Molecular cancer · 2018Review
- Chloride Influx of Anion Exchanger 2 Was Modulated by Calcium-Dependent Spinophilin in Submandibular Glands.Frontiers in physiology · 2018Article
- Coordinated downregulation of Spinophilin and the catalytic subunits of PP1, PPP1CA/B/C, contributes to a worse prognosis in lung cancer.Oncotarget · 2017Article
- NAMPT overexpression induces cancer stemness and defines a novel tumor signature for glioma prognosis.Oncotarget · 2017Article
- The Cytoskeletal Adapter Protein Spinophilin Regulates Invadopodia Dynamics and Tumor Cell Invasion in Glioblastoma.Molecular cancer research : MCR · 2016Article
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The spinophilin (Spn, PPP1R9B) gene is located at 17q21.33, a region frequently associated with microsatellite instability and loss of heterozygosity, especially in breast tumors. Spn is a regulatory subunit of phosphatase1a (PP1), which targets the catalytic subunit to distinct subcellular locations. Spn downregulation reduces PPP1CA activity against the retinoblastoma protein, pRb, thereby maintaining higher levels of phosphorylated pRb. This effect contributes to an increase in the tumorigenic properties of cells in certain contexts. Here, we explored the mechanism of how Spn downregulation contributes to the malignant phenotype and poor prognosis in breast tumors and found an increase in the stemness phenotype. Analysis of human breast tumors showed that Spn mRNA and protein are reduced or lost in 15% of carcinomas, correlating with a worse prognosis, a more aggressive tumor phenotype and triple-negative tumors, whereas luminal tumors showed high Spn levels. Downregulation of Spn by shRNA increased the stemness properties along with the expression of stem-related genes (Sox2, KLF4, Nanog and OCT4), whereas ectopic overexpression of Spn cDNA reduced these properties. Breast tumor stem cells appeared to have low levels of Spn mRNA, and Spn loss correlated with increased stem-like cell appearance in breast tumors as indicated by an increase in CD44+/CD24- cells. A reduction of the levels of PPP1CA mimicked the cancer stem-like cell phenotype of Spn downregulation, suggesting that the mechanism of Spn involves PP1a. These increased cancer stem cell-like properties with reduced Spn might account for the malignant phenotype observed in Spn-loss tumors and may contribute to a worse patient prognosis.
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