Notch activation suppresses fibroblast growth factor-dependent cellular transformation

56Citations
Citations of this article
58Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Aberrant activations of the Notch and fibroblast growth factor receptor (FGFR) signaling pathways have been correlated with neoplastic growth in humans and other mammals. Here we report that the suppression of Notch signaling in NIH 3T3 cells by the expression of either the extracellular domain of the Notch ligand Jaggedl or dominant-negative forms of Notch1 and Notch2 results in the appearance of an exaggerated fibroblast growth factor (FGF)-dependent transformed phenotype characterized by anchorage-independent growth in soft agar. Anchorage-independent growth exhibited by Notch-repressed NIH 3T3 cells may result from prolonged FGFR stimulation caused by both an increase in the expression of prototypic and oncogenic FGF gene family members and the nonclassical export of FGF1 into the extracellular compartment. Interestingly, FGF exerts a negative effect on Notch by suppressing CSL (CBF-1/RBP-Jk/KBF2 in mammals, Su(H) in Drosophila and Xenopus, and Lag-2 in Caenorhabditis elegans)-dependent transcription, and the ectopic expression of constitutively active forms of Notch1 or Notch2 abrogates FGF1 release and the phenotypic effects of FGFR stimulation. These data suggest that communication between the Notch and FGFR pathways may represent an important reciprocal autoregulatory mechanism for the regulation of normal cell growth.

Cite

CITATION STYLE

APA

Small, D., Kovalenko, D., Soldi, R., Mandinova, A., Kolev, V., Trifonova, R., … Maciag, T. (2003). Notch activation suppresses fibroblast growth factor-dependent cellular transformation. Journal of Biological Chemistry, 278(18), 16405–16413. https://doi.org/10.1074/jbc.M300464200

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free