Met receptor tyrosine kinase transactivation is involved in proteinase-activated receptor-2-mediated hepatocellular carcinoma cell invasion

被引：37

作者：

Kaufmann, Roland ^{[1
]}

Oettel, Claudia

Horn, Antje

Halbhuber, Karl-Juergen ^{[2
]}

Eitner, Annett ^{[2
]}

Krieg, Reimar ^{[2
]}

Katenkamp, Kathrin ^{[3
]}

Henklein, Peter ^{[4
]}

Westermann, Martin ^{[5
]}

Boehmer, Frank D. ^{[6
]}

Ramachandran, Rithwik ^{[7
]}

Saifeddine, Mahmoud ^{[7
]}

Hollenberg, Morley D. ^{[7
]}

Settmacher, Utz

机构：

[1] Univ Jena, Res Lab, Dept Gen Visceral & Vasc Surg, Res Ctr Lobeda,Med Fac, D-07747 Jena, Germany

[2] Univ Jena, Inst Anat 2, Fac Med, D-07743 Jena, Germany

[3] Univ Jena, Inst Pathol, Fac Med, D-07743 Jena, Germany

[4] Humboldt Univ, Inst Biochem, Charite, D-10117 Berlin, Germany

[5] Univ Jena, Ctr Electron Microscopy, Fac Med, D-07743 Jena, Germany

[6] Univ Jena, Inst Mol Cell Biol, Fac Med, D-07743 Jena, Germany

[7] Univ Calgary, Canadian Inst Hlth Res Proteinases & Inflammat Ne, Inflammat Res Network, Dept Pharmacol & Therapeut, Calgary, AB T2N 4N1, Canada

来源：

CARCINOGENESIS | 2009年 / 30卷 / 09期

基金：

加拿大健康研究院;

关键词：

GROWTH-FACTOR RECEPTOR; THROMBIN RECEPTOR; COUPLED RECEPTORS; MOLECULAR-CLONING; COLON-CANCER; FACTOR VIIA; MAP KINASE; EXPRESSION; MIGRATION; PROLIFERATION;

D O I：

10.1093/carcin/bgp153

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The expression of proteinase-activated receptor (PAR)(2) in human hepatocellular carcinoma (HCC) was established by reverse transcription-polymerase chain reaction, confocal immunofluorescence and electron microscopy in permanent cell lines, primary HCC cell cultures and HCC tumor tissue. Stimulation of HCC cells with trypsin and the PAR(2)-selective activating peptide, 2-furoyl-LIGRLO-NH2, increased cell invasion across Matrigel. Both effects were blocked by a PAR(2)-selective pepducin antagonist peptide (pal-PAR(2)) and by PAR(2) silencing with specific small interfering RNA (siRNA). PAR(2)-initiated HCC cell invasion was also blocked by inhibiting the hepatocyte growth factor receptor (Met receptor tyrosine kinase) with the receptor-targeted kinase inhibitors, SU 11274 and PHA 665752, or by downregulation of Met with specific siRNA. The involvement of Met in PAR(2)-mediated HCC invasive signaling was further supported by the finding that treatment of HCC cells with trypsin or the PAR(2)-selective agonist peptide, 2-furoyl-LIGRLO-NH2, stimulated Met activation-phosphorylation. In addition, Met-dependent stimulation of p42/p44 mitogen-activated protein Kinases was found to be critical for the PAR(2)-Met receptor tyrosine kinase-invasive signaling axis in HCC cells. Our study establishes an important link between the PAR(2) and Met receptor tyrosine kinase signaling in promoting HCC cell invasion.

引用

页码：1487 / 1496

页数：10

共 51 条

[1]

Al-Ani B, 1999, J PHARMACOL EXP THER, V290, P753

[2]

ALBINI A, 1987, CANCER RES, V47, P3239

[3] The tumour microenvironment as a target for chemoprevention [J].