title: Serine/threonine kinase 17A is a novel candidate for therapeutic targeting in glioblastoma.
abstract: STK17A is a relatively uncharacterized member of the death-associated protein family of serine/threonine kinases which have previously been associated with cell death and apoptosis. Our prior work established that STK17A is a novel p53 target gene that is induced by a variety of DNA damaging agents in a p53-dependent manner. In this study we have uncovered an additional, unanticipated role for STK17A as a candidate promoter of cell proliferation and survival in glioblastoma (GBM). Unexpectedly, it was found that STK17A is highly overexpressed in a grade-dependent manner in gliomas compared to normal brain and other cancer cell types with the highest level of expression in GBM. Knockdown of STK17A in GBM cells results in a dramatic alteration in cell shape that is associated with decreased proliferation, clonogenicity, migration, invasion and anchorage independent colony formation. STK17A knockdown also sensitizes GBM cells to genotoxic stress. STK17A overexpression is associated with a significant survival disadvantage among patients with glioma which is independent of age, molecular phenotype, IDH1 mutation, PTEN loss, and alterations in the p53 pathway and partially independent of grade. In summary, we demonstrate that STK17A provides a proliferative and survival advantage to GBM cells and is a potential target to be exploited therapeutically in patients with glioma.
authors: Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
authors: Pingping
authors: P
authors: Mao
authors: Mary P
authors: MP
authors: Hever-Jardine
authors: Gilbert J
authors: GJ
authors: Rahme
authors: Eric
authors: E
authors: Yang
authors: Janice
authors: J
authors: Tam
authors: Anita
authors: A
authors: Kodali
authors: Bijesh
authors: B
authors: Biswal
authors: Camilo E
authors: CE
authors: Fadul
authors: Arti
authors: A
authors: Gaur
authors: Mark A
authors: MA
authors: Israel
authors: Michael J
authors: MJ
authors: Spinella
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D063646:Carcinogenesis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D058990:Molecular Targeted Therapy; D060787:Neoplasm Grading; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: D051017:Apoptosis Regulatory Proteins; D017346:Protein Serine-Threonine Kinases; C115488:STK17A protein, human