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Critical Reviews™ in Oncogenesis
SJR: 0.631 SNIP: 0.503 CiteScore™: 2

ISSN Print: 0893-9675
ISSN Online: 2162-6448

Critical Reviews™ in Oncogenesis

DOI: 10.1615/CritRevOncog.v8.i1.40
pages 71-92

The Insulin-Like Growth Factor-I Receptor Signaling Pathways Are Important for Tumorigenesis and Inhibition of Apoptosis

Haim Werner
Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University
Derek Le Roith
Diabetes Branch, NIDDK, NIH, Bethesda, Maryland

ABSTRACT

The biological actions of the insulin-like growth factors IGF-I and IGF-II are mediated by their activation of the IGF-IR, a transmembrane tyrosine kinase linked to the ras-raf-MAPK cascade. Functional IGF-IRs are required for the cell to progress through the cell cycle. Most importantly, cells lacking this receptor cannot be transformed by any of a number of dominant oncogenes, a finding that proves that the presence of the IGF-IR is important for the development of a malignant phenotype. Consistent with this role, the IGF-IR displays a potent antiapoptotic effect, both in vitro and in vivo. Because of its key role in the transformation process, the IGF-IR is actively studied as a potential therapeutic target in different types of neoplastic growth.