Melanoma cell migration to type IV collagen requires activation of NF-κB

Louis Hodgson, Andrew J. Henderson, Cheng Dong

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Chemotaxis is the consequence of environmental factors engaging their receptors to initiate signaling cascades. However, the biochemical mechanisms controlling this phenomenon are not clear. We employed an in vitro modified Boyden 48-well chemotaxis migration system to characterize the role of signal transducers in type IV collagen (CIV) induced A2058 human melanoma cell migration. Using specific pharmacological inhibitors and a series of dominant-negative and constitutively active signaling proteins, we show that Ras and Rac GTPases, PI-3K, and PKC participate in cell migration mediated by β1 integrins. Collagen also induces a time-dependent degradation of IκB-α and an increase in nuclear translocation of NF-κB which is dependent on PKC pathway. More importantly, collagen-stimulated melanoma cell migration directly correlated with an increase in NF-κB transactivation. Furthermore, CIV induced an increase in β1 integrin mRNA levels. Specific NF-κB inhibitors Helenalin and SN-50 inhibited melanoma cell migration to collagen, indicating a novel requirement for NF-κB transactivation in cell chemotaxis mediated by β1 integrin signals. These results describe signal transduction events that are initiated by type IV collagen through β1 integrins and demonstrate an important role for NF-κB in regulating melanoma chemotaxis.

Original languageEnglish (US)
Pages (from-to)98-108
Number of pages11
JournalOncogene
Volume22
Issue number1
DOIs
StatePublished - Jan 9 2003
Externally publishedYes

Fingerprint

Collagen Type IV
Chemotaxis
Integrins
Cell Movement
Melanoma
Collagen
Transcriptional Activation
rac GTP-Binding Proteins
ras Proteins
Transducers
Phosphatidylinositol 3-Kinases
Signal Transduction
Pharmacology
Messenger RNA

Keywords

  • A2058
  • Chemotaxis
  • GTPase
  • Integrin
  • Transactivation

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Melanoma cell migration to type IV collagen requires activation of NF-κB. / Hodgson, Louis; Henderson, Andrew J.; Dong, Cheng.

In: Oncogene, Vol. 22, No. 1, 09.01.2003, p. 98-108.

Research output: Contribution to journalArticle

Hodgson, Louis ; Henderson, Andrew J. ; Dong, Cheng. / Melanoma cell migration to type IV collagen requires activation of NF-κB. In: Oncogene. 2003 ; Vol. 22, No. 1. pp. 98-108.
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