hnRNP A1-mediated translational regulation of the G quadruplex-containing RON receptor tyrosine kinase mRNA linked to tumor progression

被引：29

作者：

Cammas, Anne ^{[1
,2
]}

Lacroix-Triki, Magali ^{[1
,2
,3
]}

Pierredon, Sandra ^{[1
,2
,3
]}

Le Bras, Morgane ^{[1
,2
]}

Iacovoni, Jason S. ^{[1
,2
]}

Teulade-Fichou, Marie-Paule ^{[4
,5
]}

Favre, Gilles ^{[1
,2
,3
]}

Roche, Henri ^{[1
,2
,3
]}

Filleron, Thomas ^{[3
]}

Millevoi, Stefania ^{[1
,2
]}

Vagner, Stephan ^{[1
,6
,7
,8
]}

机构：

[1] Ctr Rech Cancerol Toulouse, INSERM, UMR 1037, Toulouse, France

[2] Univ Toulouse 3, F-31062 Toulouse, France

[3] Inst Claudius Regaud, Toulouse, France

[4] PSL Res Univ, Inst Curie, CNRS, UMR 176, Orsay, France

[5] PSL Res Univ, Inst Curie, CNRS, UMR 3348, Orsay, France

[6] Univ Paris Saclay, Univ Paris 11, CNRS, UMR 176, Orsay, France

[7] Univ Paris Saclay, Univ Paris 11, CNRS, UMR 3348, Orsay, France

[8] Equipe Labellisee Ligue Canc, Paris, France

来源：

ONCOTARGET | 2016年 / 7卷 / 13期

关键词：

breast cancer; metastasis; RNA-binding protein; RON; translation; CANCER PROGRESSION; A1; CONTROLS; METASTASIS; INITIATION; PROTEIN; PROMOTES; CELLS; ACTIVATION; TRANSITION; TRANSPORT;

D O I：

10.18632/oncotarget.7589

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The expression and role of RNA binding proteins (RBPs) controlling mRNA translation during tumor progression remains largely uncharacterized. Analysis by immunohistochemistry of the expression of hnRNP A1, hnRNPH, RBM9/FOX2, SRSF1/ASF/SF2, SRSF2/SC35, SRSF3/SRp20, SRSF7/9G8 in breast tumors shows that the expression of hnRNP A1, but not the other tested RBPs, is associated with metastatic relapse. Strikingly, hnRNP A1, a nuclear splicing regulator, is also present in the cytoplasm of tumor cells of a subset of patients displaying exceedingly worse prognosis. Expression of a cytoplasmic mutant of hnRNP A1 leads to increased translation of the mRNA encoding the tyrosine kinase receptor RON/MTS1R, known for its function in tumor dissemination, and increases cell migration in vitro. hnRNP A1 directly binds to the 5' untranslated region of the RON mRNA and activates its translation through G-quadruplex RNA secondary structures. The correlation between hnRNP A1 and RON tumoral expression suggests that these findings hold clinical relevance.

引用

页码：16793 / 16805

页数：13

共 29 条

[1] Regulation of heterogenous nuclear ribonucleoprotein A1 transport by phosphorylation in cells stressed by osmotic shock [J].