View in EDS

The Helicase HAGE Expressed by Malignant Melanoma-Initiating Cells Is Required for Tumor Cell Proliferation in Vivo.

Saved in:
Bibliographic Details
Title: The Helicase HAGE Expressed by Malignant Melanoma-Initiating Cells Is Required for Tumor Cell Proliferation in Vivo.
Authors: Linley, Adam J.1, Mathieu, Morgan G.1, Miles, Amanda K.1, Rees, Robert C.1, McArdle, Stephanie E. B.1, Regad, Tarik1 tarik.regad@ntu.ac.uk
Source: Journal of Biological Chemistry. 4/20/2012, Vol. 287 Issue 17, p13633-13643. 11p.
Subjects: Helicases, Melanoma, Cancer cells, Tumor growth, Adenosine triphosphate, Carcinogenesis, Neuroblastoma, Laboratory mice
Abstract: Malignant melanoma-initiating cells (MMIC) are a subpopulation of cells responsible for melanoma tumor growth and progression. They are defined by the expression of the ATP-binding cassette (ABC) subfamily B member 5 (ABCB5). Here, we identified a critical role for the DEAD-box helicase antigen (HAGE) in ABCB5+ MMIC-dependent tumorigenesis and show that HAGE-specific inactivation inhibits melanoma tumor growth mediated by this tumor-initiating population. Knockdown of HAGE led to a significant decrease in RAS protein expression with a concomitant decrease in activation of the AKT and ERK signaling pathways implicated to play an important role in melanoma progression. To confirm that the reduction in NRAS (Neuroblastoma RAS) expression was dependent on the HAGE helicase activity, we showed that NRAS, effectively silenced by siRNA, could be rescued by reintroduction of HAGE in cells lacking HAGE. Furthermore, we provide a mechanism by which HAGE promotes NRAS unwinding in vitro. We also observed using tumor transplantation in Non-obese diabetic/severe combined immunodeficiency mice that the HAGE knockdown in a ABCB5+ melanoma cell line displayed a significant decrease in tumor growth and compared with the control. Our results suggest that the helicase HAGE is required for ABCB5+MMIC-dependent tumor growth through promoting RAS protein expression and that cancer therapies targeting HAGE helicase may have broad applications for treating malignant melanoma and potentially other cancer types. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
FullText Text:
  Availability: 0
Header DbId: egs
DbLabel: Engineering Source
An: 74656945
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: The Helicase HAGE Expressed by Malignant Melanoma-Initiating Cells Is Required for Tumor Cell Proliferation in Vivo.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Linley%2C+Adam+J%2E%22">Linley, Adam J.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Mathieu%2C+Morgan+G%2E%22">Mathieu, Morgan G.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Miles%2C+Amanda+K%2E%22">Miles, Amanda K.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Rees%2C+Robert+C%2E%22">Rees, Robert C.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22McArdle%2C+Stephanie+E%2E+B%2E%22">McArdle, Stephanie E. B.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Regad%2C+Tarik%22">Regad, Tarik</searchLink><relatesTo>1</relatesTo><i> tarik.regad@ntu.ac.uk</i>
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. 4/20/2012, Vol. 287 Issue 17, p13633-13643. 11p.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Helicases%22">Helicases</searchLink><br /><searchLink fieldCode="DE" term="%22Melanoma%22">Melanoma</searchLink><br /><searchLink fieldCode="DE" term="%22Cancer+cells%22">Cancer cells</searchLink><br /><searchLink fieldCode="DE" term="%22Tumor+growth%22">Tumor growth</searchLink><br /><searchLink fieldCode="DE" term="%22Adenosine+triphosphate%22">Adenosine triphosphate</searchLink><br /><searchLink fieldCode="DE" term="%22Carcinogenesis%22">Carcinogenesis</searchLink><br /><searchLink fieldCode="DE" term="%22Neuroblastoma%22">Neuroblastoma</searchLink><br /><searchLink fieldCode="DE" term="%22Laboratory+mice%22">Laboratory mice</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Malignant melanoma-initiating cells (MMIC) are a subpopulation of cells responsible for melanoma tumor growth and progression. They are defined by the expression of the ATP-binding cassette (ABC) subfamily B member 5 (ABCB5). Here, we identified a critical role for the DEAD-box helicase antigen (HAGE) in ABCB5+ MMIC-dependent tumorigenesis and show that HAGE-specific inactivation inhibits melanoma tumor growth mediated by this tumor-initiating population. Knockdown of HAGE led to a significant decrease in RAS protein expression with a concomitant decrease in activation of the AKT and ERK signaling pathways implicated to play an important role in melanoma progression. To confirm that the reduction in NRAS (Neuroblastoma RAS) expression was dependent on the HAGE helicase activity, we showed that NRAS, effectively silenced by siRNA, could be rescued by reintroduction of HAGE in cells lacking HAGE. Furthermore, we provide a mechanism by which HAGE promotes NRAS unwinding in vitro. We also observed using tumor transplantation in Non-obese diabetic/severe combined immunodeficiency mice that the HAGE knockdown in a ABCB5+ melanoma cell line displayed a significant decrease in tumor growth and compared with the control. Our results suggest that the helicase HAGE is required for ABCB5+MMIC-dependent tumor growth through promoting RAS protein expression and that cancer therapies targeting HAGE helicase may have broad applications for treating malignant melanoma and potentially other cancer types. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=egs&AN=74656945
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1074/jbc.M111.308973
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 11
        StartPage: 13633
    Subjects:
      – SubjectFull: Helicases
        Type: general
      – SubjectFull: Melanoma
        Type: general
      – SubjectFull: Cancer cells
        Type: general
      – SubjectFull: Tumor growth
        Type: general
      – SubjectFull: Adenosine triphosphate
        Type: general
      – SubjectFull: Carcinogenesis
        Type: general
      – SubjectFull: Neuroblastoma
        Type: general
      – SubjectFull: Laboratory mice
        Type: general
    Titles:
      – TitleFull: The Helicase HAGE Expressed by Malignant Melanoma-Initiating Cells Is Required for Tumor Cell Proliferation in Vivo.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Linley, Adam J.
      – PersonEntity:
          Name:
            NameFull: Mathieu, Morgan G.
      – PersonEntity:
          Name:
            NameFull: Miles, Amanda K.
      – PersonEntity:
          Name:
            NameFull: Rees, Robert C.
      – PersonEntity:
          Name:
            NameFull: McArdle, Stephanie E. B.
      – PersonEntity:
          Name:
            NameFull: Regad, Tarik
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 20
              M: 04
              Text: 4/20/2012
              Type: published
              Y: 2012
          Identifiers:
            – Type: issn-print
              Value: 00219258
          Numbering:
            – Type: volume
              Value: 287
            – Type: issue
              Value: 17
          Titles:
            – TitleFull: Journal of Biological Chemistry
              Type: main
ResultId 1