Endothelins and hypoxia-inducible factor in cancer.

Abstract:

:The endothelin system is a family of three similar small peptides, two G-protein-coupled receptors and two proteinases. Endothelins have several physiological roles, notably in embryonic differentiation and vascular homeostasis. Numerous types of tumour express endothelins and their regulation is often aberrant when compared with the normal tissue from which the tumour arose. However, endothelin expression is tumour-type specific, and in some instances, expression of individual members of the endothelin system will be upregulated, while in other tumour types, they may be downregulated. Endothelins have numerous potential roles in tumours including modulating angiogenesis, inducing mitogenesis and invasion of tumour cells, and protecting cells from apoptosis. Expression of endothelins is controlled by the tumour microenvironment, whilst the endothelins themselves modify that environment; a case in point is that hypoxia stimulates endothelin expression via hypoxia-inducible factor (HIF)-1, while endothelins stabilise HIF-1 leading to expression of, for instance, vascular endothelial growth factor. This review highlights the potential roles of endothelins in various cancers and describes the pre-clinical and clinical progress that has been made in several tumour types - notably prostate, ovary, melanoma and breast cancer. The interactions between the endothelin network and HIF-1 are highlighted.

journal_name

Endocr Relat Cancer

journal_title

Endocrine-related cancer

authors

Grimshaw MJ

doi

10.1677/ERC-07-0057

subject

Has Abstract

pub_date

2007-06-01 00:00:00

pages

233-44

issue

2

eissn

1351-0088

issn

1479-6821

pii

14/2/233

journal_volume

14

pub_type

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