Tie1 deficiency induces endothelial-mesenchymal transition

被引：43

作者：

Garcia, Julie ^{[1
,2
]}

Sandi, Maria Jose ^{[1
,2
]}

Cordelier, Pierre ^{[3
]}

Binetruy, Bernard ^{[4
,5
]}

Pouyssegur, Jacques ^{[6
]}

Iovanna, Juan Lucio ^{[1
,2
]}

Tournaire, Roselyne ^{[1
,2
]}

机构：

[1] INSERM, U624, F-13288 Marseille, France

[2] Univ Aix Marseille 2, Fac Sci Luminy, F-13288 Marseille, France

[3] Inst Med Mol Rangueil, INSERM I2MR 858, Dept Canc Epitheliaux Angiogenese & Signalisat, F-31432 Toulouse, France

[4] INSERM, U626, Fac Med, F-13385 Marseille, France

[5] Univ Aix Marseille 2, Fac Med, F-13385 Marseille, France

[6] Ctr Antoine Lacassagne, Inst Signaling Dev Biol & Canc, CNRS UMR 6543, F-06189 Nice, France

来源：

EMBO REPORTS | 2012年 / 13卷 / 05期

关键词：

angiogenesis; endothelial-mesenchymal transition; pancreatic cancer; Slug; Tie1; RECEPTOR-TYROSINE KINASE; PANCREATIC-CANCER; TUMOR MICROENVIRONMENT; GROWTH-FACTOR; PROGRESSION; ERK5; FIBROBLASTS; EXPRESSION; MIGRATION; ROLES;

D O I：

10.1038/embor.2012.29

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：

Endothelial-mesenchymal transition (EndMT) has a significant role in embryonic heart formation and in various pathologies. However, the molecular mechanisms that regulate EndMT induction remain to be elucidated. We show that suppression of receptor tyrosine kinase Tie1 but not Tie2 induces human endothelial cells to undergo EndMT and that Slug deficiency reverts this process. We find that Erk1/2, Erk5 and Akt cascades control Slug promoter activity induced by Tie1 deficiency. Interestingly, EndMT is present in human pancreatic tumour. We propose that EndMT associated with Tie1 downregulation participates in the pathological development of stroma observed in tumours.

引用

页码：431 / 439

页数：9

共 23 条

[1] Prognostic significance of S100A4 and vascular endothelial growth factor expression in pancreatic cancer [J].

Ai, Kai-Xing ;

Lu, Lin-Yuan ;

Huang, Xin-Yu ;

Chen, Wei ;

Zhang, Hui-Zhen .

WORLD JOURNAL OF GASTROENTEROLOGY, 2008, 14 (12) :1931-1935

[2] Erk5 Controls Slug Expression and Keratinocyte Activation during Wound Healing [J].

Arnoux, Valerie ;

Nassour, Mayssaa ;

L'Helgoualc'h, Annie ;

Hipskind, Robert A. ;

Savagner, Pierre .

MOLECULAR BIOLOGY OF THE CELL, 2008, 19 (11) :4738-4749

[3] Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system [J].

Augustin, Hellmut G. ;

Koh, Gou Young ;

Thurston, Gavin ;

Alitalo, Kari .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2009, 10 (03) :165-177

[4] VE-cadherin is not required for the fort-nation of nascent blood vessels but acts to prevent their disassembly [J].

Crosby, CV ;

Fleming, PA ;

Argraves, WS ;

Corada, M ;

Zanetta, L ;

Dejana, E ;

Drake, CJ .

BLOOD, 2005, 105 (07) :2771-2776

[5]

Deissler H, 2006, INT J MOL MED, V18, P577

[6]

Erkan M., 2010, Experimental Oncology, V32, P128

[7] The Activated Stroma Index Is a Novel and Independent Prognostic Marker in Pancreatic Ductal Adenocarcinoma [J].

Erkan, Mert ;

Michalski, Christoph W. ;

Rieder, Simon ;

Reiser-Erkan, Carolin ;

Abiatari, Ivane ;

Kolb, Armin ;

Giese, Nathalia A. ;

Esposito, Irene ;

Friess, Helmut ;

Kleeff, Joerg .

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, 2008, 6 (10) :1155-1161

[8] The role of the tumor microenvironment in the progression of pancreatic cancer [J].

Farrow, Buckminster ;

Albo, Daniel ;

Berger, David H. .

JOURNAL OF SURGICAL RESEARCH, 2008, 149 (02) :319-328

[9] ATTACHMENT OF SMOOTH-MUSCLE CELLS TO COLLAGEN AND THEIR MIGRATION TOWARD PLATELET-DERIVED GROWTH-FACTOR [J].

GROTENDORST, GR ;

SEPPA, HEJ ;

KLEINMAN, HK ;

MARTIN, GR .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1981, 78 (06) :3669-3672

[10] Targeting the ANGPT-TIE2 pathway in malignancy [J].

Huang, Hanhua ;

Bhat, Abhijit ;

Woodnutt, Gary ;

Lappe, Rodney .

NATURE REVIEWS CANCER, 2010, 10 (08) :575-585

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