Oncogenic fusion proteins adopt the insulin-like growth factor signaling pathway

Haim Werner*, Shilhav Meisel-Sharon, Ilan Bruchim

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


The insulin-like growth factor-1 receptor (IGF1R) has been identified as a potent anti-apoptotic, pro-survival tyrosine kinase-containing receptor. Overexpression of the IGF1R gene constitutes a typical feature of most human cancers. Consistent with these biological roles, cells expressing high levels of IGF1R are expected not to die, a quintessential feature of cancer cells. Tumor specific chromosomal translocations that disrupt the architecture of transcription factors are a common theme in carcinogenesis. Increasing evidence gathered over the past fifteen years demonstrate that this type of genomic rearrangements is common not only among pediatric and hematological malignancies, as classically thought, but may also provide a molecular and cytogenetic foundation for an ever-increasing portion of adult epithelial tumors. In this review article we provide evidence that the mechanism of action of oncogenic fusion proteins associated with both pediatric and adult malignancies involves transactivation of the IGF1R gene, with ensuing increases in IGF1R levels and ligand-mediated receptor phosphorylation. Disrupted transcription factors adopt the IGF1R signaling pathway and elicit their oncogenic activities via activation of this critical regulatory network. Combined targeting of oncogenic fusion proteins along with the IGF1R may constitute a promising therapeutic approach.

Original languageEnglish
Article number28
JournalMolecular Cancer
Issue number1
StatePublished - 19 Feb 2018


FundersFunder number
Israel Science Foundation


    • Chimeric fusion proteins
    • Disrupted transcription factors
    • IGF1 receptor (IGF1R)
    • Insulin-like growth factor-1 (IGF1)
    • Transcription


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