title: PTK7 regulates Id1 expression in CD44-high glioma cells.
abstract: BACKGROUND
  CD44 is a molecular marker associated with molecular subtype and treatment resistance in glioma. More effective therapies will result from approaches aimed at targeting the CD44-high gliomas.
  
  
  METHODS
  Protein tyrosine kinase 7 (PTK7) mRNA expression was analyzed based on The Cancer Genome Atlas glioblastoma dataset. PTK7 expression was depleted through lentivirus-mediated short hairpin RNA knockdown. Terminal deoxynucleotidyl transferase dUTP nick-end labeling was used to evaluate cell apoptosis following PTK7 knockdown. Gene expression analysis was performed on Affymetrix microarray. A nude mice orthotopic tumor model was used to evaluate the in vivo effect of PTK7 depletion.
  
  
  RESULTS
  PTK7 is highly expressed in CD44-high glioblastoma and predicts unfavorable prognosis. PTK7 knockdown attenuated cell proliferation, impaired tumorigenic potential, and induced apoptosis in CD44-high glioma cell lines. Gene expression analysis identified inhibitor of DNA Binding 1 (Id1) gene as a potential downstream effector for PTK7. Overexpression of Id1 mostly restored the cell proliferation and colony formation attenuated by PTK7 depletion. PTK7 enhanced anchorage-independent growth in normal human astrocytes, which was attenuated by Id1 knockdown. Furthermore, PTK7 regulated Id1 expression through modulating TGF-β/Smad signaling, while pharmacological inhibition on TGF-β/Smad signaling or PTK7/Id1 depletion attenuated TGF-β-stimulated cell proliferation. PTK7 depletion consistently reduced Id1 expression, suppressed tumor growth, and induced apoptosis in a murine orthotopic tumor model, which could be translated into prolonged survival in tumor-bearing mice.
  
  
  CONCLUSIONS
  PTK7 regulates Id1 expression in CD44-high glioma cell lines. Targeting PTK7 could be an effective strategy for treating glioma with high CD44 expression.
authors.affiliation: Department of Neurosurgery, Central South University, Hunan, China (Q.L, C.Z., J.Y., J.F., J.S., X.W., X.Y., W.J.); The Institute of Skull Base Surgery and Neurooncology at Hunan, China (Q.L., J.Y., J.F., X.Y., W.J.); Cancer Research Institute, Central South University, Hunan, China (M.W.).
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Central South University, Hunan, China (Q.L, C.Z., J.Y., J.F., J.S., X.W., X.Y., W.J.); The Institute of Skull Base Surgery and Neurooncology at Hunan, China (Q.L., J.Y., J.F., X.Y., W.J.); Cancer Research Institute, Central South University, Hunan, China (M.W.).
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Central South University, Hunan, China (Q.L, C.Z., J.Y., J.F., J.S., X.W., X.Y., W.J.); The Institute of Skull Base Surgery and Neurooncology at Hunan, China (Q.L., J.Y., J.F., X.Y., W.J.); Cancer Research Institute, Central South University, Hunan, China (M.W.).
authors.forename: Jian
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Neurosurgery, Central South University, Hunan, China (Q.L, C.Z., J.Y., J.F., J.S., X.W., X.Y., W.J.); The Institute of Skull Base Surgery and Neurooncology at Hunan, China (Q.L., J.Y., J.F., X.Y., W.J.); Cancer Research Institute, Central South University, Hunan, China (M.W.).
authors.forename: Jun
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Neurosurgery, Central South University, Hunan, China (Q.L, C.Z., J.Y., J.F., J.S., X.W., X.Y., W.J.); The Institute of Skull Base Surgery and Neurooncology at Hunan, China (Q.L., J.Y., J.F., X.Y., W.J.); Cancer Research Institute, Central South University, Hunan, China (M.W.).
authors.forename: Minghua
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Central South University, Hunan, China (Q.L, C.Z., J.Y., J.F., J.S., X.W., X.Y., W.J.); The Institute of Skull Base Surgery and Neurooncology at Hunan, China (Q.L., J.Y., J.F., X.Y., W.J.); Cancer Research Institute, Central South University, Hunan, China (M.W.).
authors.forename: Jun
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Neurosurgery, Central South University, Hunan, China (Q.L, C.Z., J.Y., J.F., J.S., X.W., X.Y., W.J.); The Institute of Skull Base Surgery and Neurooncology at Hunan, China (Q.L., J.Y., J.F., X.Y., W.J.); Cancer Research Institute, Central South University, Hunan, China (M.W.).
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Central South University, Hunan, China (Q.L, C.Z., J.Y., J.F., J.S., X.W., X.Y., W.J.); The Institute of Skull Base Surgery and Neurooncology at Hunan, China (Q.L., J.Y., J.F., X.Y., W.J.); Cancer Research Institute, Central South University, Hunan, China (M.W.).
authors.forename: Xianrui
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Neurosurgery, Central South University, Hunan, China (Q.L, C.Z., J.Y., J.F., J.S., X.W., X.Y., W.J.); The Institute of Skull Base Surgery and Neurooncology at Hunan, China (Q.L., J.Y., J.F., X.Y., W.J.); Cancer Research Institute, Central South University, Hunan, China (M.W.).
authors.forename: Weixi
authors.initials: W
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000906:Antibodies; D017209:Apoptosis; D015415:Biomarkers; D001932:Brain Neoplasms / Q000201:enzymology / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015870:Gene Expression; D005909:Glioblastoma / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology / Q000378:metabolism*; D051798:Inhibitor of Differentiation Protein 1 / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D051379:Mice; D008819:Mice, Nude; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000906:Antibodies; D015415:Biomarkers; C497483:CD44 protein, human; D015815:Cell Adhesion Molecules; D018960:Hyaluronan Receptors; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; C096905:PTK7 protein, human; D020794:Receptor Protein-Tyrosine Kinases
keywords: CD44; PTK7; cell proliferation; glioma; tumorigenesis