RETRACTED: Hypoxia-inducible Factor 1 (HIF-1) Promotes Extracellular Matrix Remodeling under Hypoxic Conditions by Inducing P4HA1, P4HA2, and PLOD2 Expression in Fibroblasts (Retracted Article)

被引：387

作者：

Gilkes, Daniele M. ^{[1
,2
,8
]}

Bajpai, Saumendra ^{[8
,9
]}

Chaturvedi, Pallavi ^{[1
,2
]}

Wirtz, Denis ^{[8
,9
]}

Semenza, Gregg L. ^{[1
,2
,3
,4
,5
,6
,7
,8
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Vasc Program, Inst Cell Engn, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[6] Johns Hopkins Univ, Sch Med, Dept Radiat Oncol, Baltimore, MD 21205 USA

[7] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA

[8] Johns Hopkins Univ, Ctr Oncol, Baltimore, MD 21218 USA

[9] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2013年 / 288卷 / 15期

基金：

美国国家卫生研究院;

关键词：

SYNDROME TYPE-VI; BREAST-CANCER; LYSYL HYDROXYLASE; PROLYL; 4-HYDROXYLASES; MAMMARY-TUMORS; FACTOR-I; COLLAGEN; METASTASIS; FIBROSIS; GROWTH;

D O I：

10.1074/jbc.M112.442939

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Extracellular matrix (ECM) composition, organization, and compliance provide both architectural and chemical cues that modulate tissue structure and function. ECM produced by stromal fibroblasts plays a key role in breast cancer invasion and metastasis, which are also stimulated by intratumoral hypoxia. Here, we demonstrate that hypoxia-inducible factor 1 (HIF-1) is a critical regulator of ECM remodeling by fibroblasts under hypoxic conditions. HIF-1 activates expression of genes encoding collagen prolyl (P4HA1 and P4HA2) and lysyl (PLOD2) hydroxylases. P4HA1 and P4HA2 are required for collagen deposition, whereas PLOD2 is required for ECM stiffening and collagen fiber alignment. Together P4HA1, P4HA2, and PLOD2 mediate remodeling of ECM composition, alignment, and mechanical properties in response to hypoxia. HIF-1-dependent ECM remodeling by hypoxic fibroblasts induces changes in breast cancer cell morphology, adhesion, and motility that promote invasion and metastasis.

引用

页码：10819 / 10829

页数：11

共 54 条

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