title: Silencing of PTK7 in colon cancer cells: caspase-10-dependent apoptosis via mitochondrial pathway.
abstract: Protein tyrosine kinase-7 (PTK7) is a catalytically inactive receptor tyrosine kinase (RTK). PTK7 is upregulated in many common human cancers, including colon cancer, lung cancer, gastric cancer and acute myeloid leukemia. The reason for this up-regulation is not yet known. To explore the functional role of PTK7, the expression of PTK7 in HCT 116 cells was examined using small interference (siRNA)-mediated gene silencing. Following transfection, the siRNA successfully suppressed PTK7 mRNA and protein expression. Knocking down of PTK7 in HCT 116 cells inhibited cell proliferation compared to control groups and induced apoptosis. Furthermore, this apoptosis was characterized by decreased mitochondrial membrane potential and activation of caspase-9 and -10. Addition of a caspase-10 inhibitor totally blocked this apoptosis, suggesting that caspase-10 may play a critical role in PTK7-knockdown-induced apoptosis, downstream of mitochondria. These observations may indicate a role for PTK7 in cell proliferation and cell apoptosis and may provide a potential therapeutic pathway for the treatment of a variety of cancers.
authors.affiliation: Department of Chemistry, Shands Cancer Center, UF Genetics Institute, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Ling
authors.initials: L
authors.lastname: Meng
authors.forename: Kwame
authors.initials: K
authors.lastname: Sefah
authors.forename: Meghan B
authors.initials: MB
authors.lastname: O'Donoghue
authors.forename: Guizhi
authors.initials: G
authors.lastname: Zhu
authors.forename: Dihua
authors.initials: D
authors.lastname: Shangguan
authors.forename: Afshan
authors.initials: A
authors.lastname: Noorali
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Weihong
authors.initials: W
authors.lastname: Tan
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D053455:Caspase 10 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D004789:Enzyme Activation; D005434:Flow Cytometry; D045325:HCT116 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D009154:Mutation; D034622:RNA Interference; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D016159:Tumor Suppressor Protein p53; C096905:PTK7 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D053455:Caspase 10; D053453:Caspase 9