Fumarate hydratase deficiency and cancer: Activation of hypoxia signaling?

被引：29

作者：

Ratcliffe, Peter J. ^{[1
]}

机构：

[1] Univ Oxford, Oxford OX3 7BN, England

来源：

CANCER CELL | 2007年 / 11卷 / 04期

关键词：

D O I：

10.1016/j.ccr.2007.03.015

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Molecular genetic analysis of hereditary leiomyomatosis and renal cell cancer (HLRCC) unexpectedly revealed germline defects in the gene encoding the Krebs cycle enzyme fumarate hydratase (FH), stimulating great interest in the underlying mechanism of oncogenesis. It has been proposed that the associated accumulation of fumarate competitively inhibits the 2-oxoglutarate-dependent dioxygenases that regulate hypoxia-inducible factor (HIF), thus activating oncogenic hypoxia pathways. In this issue of Cancer Cell Pollard and colleagues describe a genetic mouse model of FH deficiency that recapitulates aspects of the human disease, including HIF activation and renal cysts, enabling further insights into this unusual cancer syndrome.

引用

收藏

页码：303 / 305

页数：3

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