title: Kinase-Dependent and -Independent Roles for PTK6 in Colon Cancer.
abstract: Disruption of the gene encoding Protein Tyrosine Kinase 6 (Ptk6) delayed differentiation and increased growth in the mouse intestine. However, Ptk6-null mice were also resistant to azoxymethane-induced colon tumorigenesis. To further explore functions of PTK6 in colon cancer, expression of epithelial and mesenchymal markers, as well as proliferation, migration, and xenograft tumor growth, was examined in human colon tumor cell lines with knockdown or overexpression of PTK6. PTK6 protein, transcript, and activation were also examined in a human colon tumor tissue array, using immunohistochemistry and qRT-PCR. Knockdown of PTK6 led to the epithelial-mesenchymal transition (EMT) in SW480 and HCT116 cells, whereas overexpression of PTK6 in SW620 cells restored an epithelial phenotype in a kinase-independent manner. PTK6 knockdown also increased xenograft tumor growth of SW480 cells, suggesting tumor suppressor functions. In clinical specimens, PTK6 expression was highest in normal differentiated epithelial cells and reduced in tumors. In contrast, overexpression of constitutively active PTK6 promoted STAT3 and ERK5 activation in colon cancer cells, and endogenous PTK6 promoted cell survival and oncogenic signaling in response to DNA-damaging treatments. These data indicate that PTK6 has complex, context-specific functions in colon cancer; PTK6 promotes the epithelial phenotype to antagonize the EMT in a kinase-independent manner, whereas activation of PTK6 promotes oncogenic signaling.
  
  
  
  Understanding context-specific functions of PTK6 is important, because although it promotes cell survival and oncogenic signaling after DNA damage, expression of PTK6 in established tumors may maintain the epithelial phenotype, preventing tumor progression. Mol Cancer Res; 14(6); 563-73. ©2016 AACR.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Priya S
authors.initials: PS
authors.lastname: Mathur
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Gierut
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Grace
authors.initials: G
authors.lastname: Guzman
authors.affiliation: Department of Epidemiology and Biostatistics, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Internal Medicine, Yale University, New Haven, Connecticut.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Xicola
authors.affiliation: Department of Internal Medicine, Yale University, New Haven, Connecticut.
authors.forename: Xavier
authors.initials: X
authors.lastname: Llor
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Chastkofsky
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Ansu O
authors.initials: AO
authors.lastname: Perekatt
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois. atyner@uic.edu.
authors.forename: Angela L
authors.initials: AL
authors.lastname: Tyner
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005260:Female; D045325:HCT116 Cells; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D009363:Neoplasm Proteins; D011505:Protein-Tyrosine Kinases; C088375:PTK6 protein, human