title: ING4 regulates JWA in angiogenesis and their prognostic value in melanoma patients.
abstract: BACKGROUND
  We previously showed that inhibitor of growth family member 4 (ING4) inhibits melanoma angiogenesis, and JWA suppresses the metastasis of melanoma cells. As angiogenesis is essential for tumour metastasis, further investigation of the function of ING4 and JWA in melanoma angiogenesis is needed, and their prognostic value are of great interest.
  
  
  METHODS
  Western blot, tube-formation assays and luciferase assays were used to investigate the correlation between ING4 and JWA in melanoma angiogenesis. JWA and integrin-linked kinase (ILK) expression was determined on a tissue microarray constructed from 175 biopsies.
  
  
  RESULTS
  ING4 promoted JWA expression by activating JWA promoter. Furthermore, the regulation of growth and tube formation of endothelial cells by ING4 was partially JWA dependent. Also, ING4 inhibited the ILK-induced angiogenesis signalling pathway via JWA. Moreover, reduced JWA, or increased ILK, expression was closely associated with 5-year disease-specific survival of melanoma patients (P=0.001 and 0.007, respectively). There was also a positive correlation between ING4 and JWA yet a negative correlation between ING4 and ILK. Importantly, their concomitant expressions were significantly related to 5-year survival of melanoma patients (P=0.002 and 0.003, respectively).
  
  
  CONCLUSIONS
  JWA has an important role in ING4-regulated melanoma angiogenesis, and ING4/JWA/ILK are promising prognostic markers and may be used as anti-angiogenic therapeutic targets for melanoma.
authors.affiliation: 1] Department of Dermatology and Skin Science, Research Pavilion, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada [2] Department of Pathophysiology, Basic Medical College, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.forename: Y
authors.initials: Y
authors.lastname: Tang
authors.forename: Y
authors.initials: Y
authors.lastname: Cheng
authors.forename: G
authors.initials: G
authors.lastname: Zhang
authors.forename: A
authors.initials: A
authors.lastname: Yip
authors.forename: M
authors.initials: M
authors.lastname: Martinka
authors.forename: Z
authors.initials: Z
authors.lastname: Dong
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: G
authors.initials: G
authors.lastname: Li
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D018797:Cell Cycle Proteins / Q000032:analysis / Q000502:physiology*; D002478:Cells, Cultured; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D057809:HEK293 Cells; D006360:Heat-Shock Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000032:analysis / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D008545:Melanoma / Q000098:blood supply / Q000175:diagnosis* / Q000235:genetics; D026901:Membrane Transport Proteins; D009389:Neovascularization, Pathologic / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000502:physiology; D012878:Skin Neoplasms / Q000098:blood supply / Q000175:diagnosis* / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000502:physiology*
chemical_list: C484566:ARL6IP5 protein, human; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D006360:Heat-Shock Proteins; D018398:Homeodomain Proteins; C483230:ING4 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D026901:Membrane Transport Proteins; D025521:Tumor Suppressor Proteins