Galectin-3 contributes to melanoma growth and metastasis via regulation of NFAT1 and autotaxin

Russell R. Braeuer, Maya Zigler, Takafumi Kamiya, Andrey S. Dobroff, Li Huang, Woonyoung Choi, David J. McConkey, Einav Shoshan, Aaron K. Mobley, Renduo Song, Avraham Raz, Menashe Bar-Eli

Research output: Contribution to journalArticle

Abstract

Melanoma is the deadliest form of skin cancer in which patients with metastatic disease have a 5-year survival rate of less than 10%. Recently, the overexpression of a b-galactoside binding protein, galectin-3 (LGALS3), has been correlated with metastatic melanoma in patients. We have previously shown that silencing galectin-3 in metastatic melanoma cells reduces tumor growth and metastasis. Gene expression profiling identified the protumorigenic gene autotaxin ( ENPP2) to be downregulated after silencing galectin-3. Here we report that galectin-3 regulates autotaxin expression at the transcriptional level by modulating the expression of the transcription factor NFAT1 (NFATC2). Silencing galectin-3 reduced NFAT1 protein expression, which resulted in decreased autotaxin expression and activity. Reexpression of autotaxin in galectin-3 silenced melanoma cells rescues angiogenesis, tumor growth, and metastasis in vivo. Silencing NFAT1 expression in metastatic melanoma cells inhibited tumor growth and metastatic capabilities in vivo. Our data elucidate a previously unidentified mechanism by which galectin-3 regulates autotaxin and assign a novel role for NFAT1 during melanoma progression.

Original languageEnglish (US)
Pages (from-to)5757-5766
Number of pages10
JournalCancer Research
Volume72
Issue number22
DOIs
StatePublished - Nov 15 2012
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Braeuer, R. R., Zigler, M., Kamiya, T., Dobroff, A. S., Huang, L., Choi, W., McConkey, D. J., Shoshan, E., Mobley, A. K., Song, R., Raz, A., & Bar-Eli, M. (2012). Galectin-3 contributes to melanoma growth and metastasis via regulation of NFAT1 and autotaxin. Cancer Research, 72(22), 5757-5766. https://doi.org/10.1158/0008-5472.CAN-12-2424