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Notch Signaling in Breast Cancer and Tumor Angiogenesis: Cross-Talk and Therapeutic Potentials

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Notch signaling is an evolutionarily conserved pathway that regulates numerous physiological processes. Disruption of Notch has been implicated in multiple tumor types. Evidence from in vitro experiments, mouse models and human tumor samples indicates that Notch plays a predominantly oncogenic role in breast cancer and interacts with other pathways involved in tumorigenesis. In addition, Notch signaling is required for physiological angiogenesis and may promote tumor angiogenesis. A variety of strategies for blocking Notch signaling, in particular γ-secretase inhibition, are discussed as potential therapies for breast cancer and tumor angiogenesis.

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Abbreviations

Dll4:

Delta-like 4

Jag1:

Jagged1

RAM:

RBP-jκ associated module

N-ICD:

Notch intracellular domain

TACE:

TNFα converting enzyme

RBP:

re-combination-signal binding protein

CSL:

CBF1, Suppressor of Hairless or Lag-1

Hes:

hairy/enhancer of split

Hey:

hairy/enhancer of split related with YRPW motif

GSI:

γ-secretase inhibitor

HIF:

hypoxia inducible factor

VEGF:

vascular endothelial growth factor

MMTV:

mouse mammary tumor virus

APC:

adenomatous polyposis coli

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Acknowledgments

Research in the lab of A.L.H. is funded by Cancer Research UK and the Sixth Framework Program of the European Union (Angiotargeting). W.S. is a Rhodes Scholar. We would like to thank Drs. Ji-Liang Li, Richard Sainson, Laura Harrington, John Moore and Ms. Cassin Williams for helpful discussions.

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  1. Molecular Oncology Laboratories, Cancer Research UK, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Headington, Oxford, OX3 9DS, UK

    Wen Shi & Adrian L. Harris

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Correspondence to Adrian L. Harris.

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Shi, W., Harris, A.L. Notch Signaling in Breast Cancer and Tumor Angiogenesis: Cross-Talk and Therapeutic Potentials. J Mammary Gland Biol Neoplasia 11, 41–52 (2006). https://doi.org/10.1007/s10911-006-9011-7

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