RT Journal Article
T1 Coordinated downregulation of Spinophilin and the catalytic subunits of PP1, PPP1CA/B/C, contributes to a worse prognosis in lung cancer
A1 Verdugo-Sivianes, Eva M.
A1 Navas, Lola
A1 Molina-Pinelo, Sonia
A1 Ferrer, Irene
A1 Quintanal-Villalonga, Alvaro
A1 Peinado, Javier
A1 Garcia-Heredia, Jose M.
A1 Felipe-Abrio, Blanca
A1 Munoz-Galvan, Sandra
A1 Marin, Juan J.
A1 Montuenga, Luis
A1 Paz-Ares, Luis
A1 Carnero, Amancio
K1 Spinophilin
K1 PP1
K1 biomarker
K1 lung cancer
K1 therapy
K1 Tumor-suppressor spinophilin
K1 Genetic-linkage analysis
K1 Cells in-vitro
K1 Breast-cancer
K1 Retinoblastoma protein
K1 Dendritic spines
K1 Chromosome 17q12-21
K1 Binding-protein
K1 Familial breast
K1 Poor-prognosis
AB The scaffold protein Spinophilin (Spinophilin, PPP1R9B) is one of the regulatory subunits of phosphatase-1 (PP1), directing it to distinct subcellular locations and targets. The loss of Spinophilin reduces PP1 targeting to pRb, thereby maintaining higher levels of phosphorylated pRb. Spinophilin is absent or reduced in approximately 40% of human lung tumors, correlating with the malignant grade. However, little is known about the relevance of the coordinated activity or presence of Spinophilin and its reported catalytic partners in the prognosis of lung cancer. In the present work, we show that the downregulation of Spinophilin, either by protein or mRNA, is related to a worse prognosis in lung tumors. This effect is more relevant in squamous cell carcinoma, SCC, than in adenocarcinoma. Downregulation of Spinophilin is related to a decrease in the levels of its partners PPP1CA/B/C, the catalytic subunits of PP1. A decrease in these subunits is also related to prognosis in SCC and, in combination with a decrease in Spinophilin, are markers of a poor prognosis in these tumors. The analysis of the genes that correlate to Spinophilin in lung tumors showed clear enrichment in ATP biosynthesis and protein degradation GO pathways. The analysis of the response to several common and pathway-related drugs indicates a direct correlation between the Spinophilin/PPP1Cs ratio and the response to oxaliplatin and bortezomib. This finding indicates that this ratio may be a good predictive biomarker for the activity of the drugs in these tumors with a poor prognosis.
PB Impact journals llc
SN 1949-2553
YR 2017
FD 2017-12-01
LK http://hdl.handle.net/10668/19447
UL http://hdl.handle.net/10668/19447
LA en
DS RISalud
RD Apr 11, 2025