RETRACTED: Hypoxia-inducible factors mediate coordinated RhoA-ROCK1 expression and signaling in breast cancer cells (Retracted Article)

被引：161

作者：

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

Xiang, Lisha ^{[1
,2
]}

Lee, Sun Joo ^{[1
,2
]}

Chaturvedi, Pallavi ^{[1
,2
]}

Hubbi, Maimon E. ^{[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, McKusick Nathans Inst Genet Med, 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, Johns Hopkins Phys Sci Oncol Ctr, Baltimore, MD 21218 USA

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

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2014年 / 111卷 / 03期

关键词：

cytoskeletal reprogramming; metastasis; migration; oxygen; tumor microenvironment; FOCAL ADHESION KINASE; RHO-ASSOCIATED KINASE; GENE-EXPRESSION; TUMOR HYPOXIA; ROCK-I; METASTASIS; FACTOR-1-ALPHA; INVASION; DENSITY; OVEREXPRESSION;

D O I：

10.1073/pnas.1321510111

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Overexpression of Rho kinase 1 (ROCK1) and the G protein RhoA is implicated in breast cancer progression, but oncogenic mutations are rare, and the molecular mechanisms that underlie increased ROCK1 and RhoA expression have not been determined. RhoA-bound ROCK1 phosphorylates myosin light chain (MLC), which is required for actin-myosin contractility. RhoA also activates focal adhesion kinase (FAK) signaling. Together, these pathways are critical determinants of the motile and invasive phenotype of cancer cells. We report that hypoxia-inducible factors coordinately activate RhoA and ROCK1 expression and signaling in breast cancer cells, leading to cell and matrix contraction, focal adhesion formation, and motility through phosphorylation of MLC and FAK. Thus, intratumoral hypoxia acts as an oncogenic stimulus by triggering hypoxia-inducible factor -> RhoA -> ROCK1 -> MLC -> FAK signaling in breast cancer cells.

引用

页码：E384 / E393

页数：10

共 59 条

[41] Gene expression profiling spares early breast cancer patients from adjuvant therapy:: derived and validated in two population-based cohorts [J].