Activation of Notch1 signaling is required for β-catenin-mediated human primary melanoma progression

Klara Balint, Min Xiao, Chelsea C. Pinnix, Akinobu Soma, Imre Veres, I. Juhász, Eric J. Brown, Anthony J. Capobianco, Meenhard Herlyn, Zhao Jun Liu

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Abstract

Notch is a highly conserved transmembrane receptor that determines cell fate. Notch signaling denotes cleavage of the Notch intracellular domain, its translocation to the nucleus, and subsequent activation of target gene transcription. Involvement of Notch signaling in several cancers is well known, but its role in melanoma remains poorly characterized. Here we show that the Notch1 pathway is activated in human melanoma. Blocking Notch signaling suppressed whereas constitutive activation of the Notch1 pathway enhanced primary melanoma cell growth both in vitro and in vivo yet had little effect on metastatic melanoma cells. Activation of Notch1 signaling enabled primary melanoma cells to gain metastatic capability. Furthermore, the oncogenic effect of Notch1 on primary melanoma cells was mediated by β-catenin, which was upregulated following Notch1 activation. Inhibiting β-catenin expression reversed Notch1-enhanced tumor growth and metastasis. Our data therefore suggest a β-catenin-dependent, stage-specific role for Notch1 signaling in promoting the progression of primary melanoma.

Original languageEnglish
Pages (from-to)3166-3176
Number of pages11
JournalJournal of Clinical Investigation
Volume115
Issue number11
DOIs
Publication statusPublished - Nov 2005

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Catenins
Melanoma
Growth
Transcriptional Activation
Neoplasms
Neoplasm Metastasis

ASJC Scopus subject areas

  • Medicine(all)

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Activation of Notch1 signaling is required for β-catenin-mediated human primary melanoma progression. / Balint, Klara; Xiao, Min; Pinnix, Chelsea C.; Soma, Akinobu; Veres, Imre; Juhász, I.; Brown, Eric J.; Capobianco, Anthony J.; Herlyn, Meenhard; Liu, Zhao Jun.

In: Journal of Clinical Investigation, Vol. 115, No. 11, 11.2005, p. 3166-3176.

Research output: Contribution to journalArticle

Balint, K, Xiao, M, Pinnix, CC, Soma, A, Veres, I, Juhász, I, Brown, EJ, Capobianco, AJ, Herlyn, M & Liu, ZJ 2005, 'Activation of Notch1 signaling is required for β-catenin-mediated human primary melanoma progression', Journal of Clinical Investigation, vol. 115, no. 11, pp. 3166-3176. https://doi.org/10.1172/JCI25001
Balint, Klara ; Xiao, Min ; Pinnix, Chelsea C. ; Soma, Akinobu ; Veres, Imre ; Juhász, I. ; Brown, Eric J. ; Capobianco, Anthony J. ; Herlyn, Meenhard ; Liu, Zhao Jun. / Activation of Notch1 signaling is required for β-catenin-mediated human primary melanoma progression. In: Journal of Clinical Investigation. 2005 ; Vol. 115, No. 11. pp. 3166-3176.
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AU - Veres, Imre

AU - Juhász, I.

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AU - Liu, Zhao Jun

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