Journal
FEBS JOURNAL
Volume 280, Issue 10, Pages 2138-2149Publisher
WILEY
DOI: 10.1111/febs.12149
Keywords
bladder cancer; cancer growth; decorin; insulin-like growth factor receptorI; signaling
Categories
Funding
- Benjamin Perkins Bladder Cancer Fund
- National Institutes of Health [RO1 CA164462, RO1 CA39481, RO1 CA47282, RO1 CA120975]
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The stromal-specific proteoglycan decorin has emerged in recent years as a critical regulator of tumor initiation and progression. Decorin regulates the biology of various types of cancer by modulating the activity of several receptor tyrosine kinases coordinating growth, survival, migration, and angiogenesis. Decorin binds to surface receptors for epidermal growth factor and hepatocyte growth factor with high affinity, and negatively regulates their activity and signaling via robust internalization and eventual degradation. The insulin-like growth factor (IGF)-I system plays a critical role in the regulation of cell growth both invivo and invitro. The IGF-I receptor (IGF-IR) is also essential for cellular transformation, owing to its ability to enhance cell proliferation and protect cancer cells from apoptosis. Recent data have pointed to a role of decorin in regulating the IGF-I system in both nontransformed and transformed cells. Significantly, there is a surprising dichotomy in the mechanism of decorin action on IGF-IR signaling, which differs considerably between physiological and pathological cellular models. In this review, we summarize the current knowledge on decorin regulation of the IGF-I system in normal and transformed cells, and discuss possible decorin-based therapeutic approaches to target IGF-IR-driven tumors.
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