Journal
CANCER RESEARCH
Volume 73, Issue 2, Pages 583-594Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-12-2447
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Funding
- Medical Research Council [G0800102]
- Institute of Cancer Research
- Cancer Research UK [C107/A10433]
- Breakthrough Breast Cancer
- NHS funding
- Scottish Academic Health Sciences Collaboration
- Scottish Government Health Department
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Identification of key molecules that drive angiogenesis is critical for the development of new modalities for the prevention of solid tumor progression. Using multiple models of colorectal cancer, we show that activity of the extracellular matrix-modifying enzyme lysyl oxidase (LOX) is essential for stimulating endothelial cells in vitro and angiogenesis in vivo. We show that LOX activates Akt through platelet-derived growth factor receptor beta (PDGFR beta) stimulation, resulting in increased VEGF expression. LOX-driven angiogenesis can be abrogated through targeting LOX directly or using inhibitors of PDGFR beta, Akt, and VEGF signaling. Furthermore, we show that LOX is clinically correlated with VEGF expression and blood vessel formation in 515 colorectal cancer patient samples. Finally, we validate our findings in a breast cancer model, showing the universality of these observations. Taken together, our findings have broad clinical and therapeutic implications for a wide variety of solid tumor types. Cancer Res; 73(2); 583-94. (C) 2012 AACR.
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