Oncogenic Kit controls neoplastic mast cell growth through a Stat5/PI3-kinase signaling cascade

被引：97

作者：

Harir, Noria ^{[2
]}

Boudot, Cedric ^{[2
]}

Friedbichler, Katrin ^{[1
]}

Sonneck, Karoline ^{[3
]}

Kondo, Rudin ^{[3
]}

Martin-Lanneree, Severine ^{[4
,5
]}

Kenner, Lukas ^{[1
,6
]}

Kerenyi, Marc ^{[7
]}

Yahiaoui, Saliha ^{[2
]}

Gouilleux-Gruart, Valerie ^{[2
]}

Gondry, Jean ^{[8
]}

Benit, Laurence ^{[4
,5
]}

Dusanter-Fourt, Isabelle ^{[4
,5
]}

Lassoued, Kaiss ^{[2
]}

Valent, Peter ^{[3
]}

Moriggl, Richard ^{[1
]}

Gouilleux, Fabrice ^{[2
]}

机构：

[1] Ludwig Boltzmann Inst Canc Res, A-1090 Vienna, Austria

[2] Univ Picardie J Verne, Fac Med, INSERM, EMI 351, Amiens, France

[3] Med Univ Vienna, Div Hematol & Hemostaseol, Dept Internal Med 1, Vienna, Austria

[4] Univ Paris 05, Inst Cochin Genet Mol, CNRS, UMR 8104, Paris, France

[5] INSERM, U567, Paris, France

[6] Med Univ Vienna, Dept Pathol, Vienna, Austria

[7] Med Univ Vienna, Div Mol Biol, Dept Med Biochem, Max F Perutz Labs, Vienna, Austria

[8] Ctr Hosp Univ, Ctr Gynecol Obstet, Amiens, France

来源：

BLOOD | 2008年 / 112卷 / 06期

基金：

奥地利科学基金会;

关键词：

D O I：

10.1182/blood-2007-09-115477

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The D816V-mutated variant of Kit triggers multiple signaling pathways and is considered essential for malignant transformation in mast cell (MC) neoplasms. We here describe that constitutive activation of the Stat5-PI3K-Akt-cascade controls neoplastic MC development. Retrovirally transduced active Stat5 (cS5F) was found to trigger PI3K and Akt activation, and to transform murine bone marrow progenitors into tissue-infiltrating MCs. Primary neoplastic Kit D816V(+) MCs in patients with mastocytosis also displayed activated Stat5, which was found to localize to the cytoplasm and to form a signaling complex with PI3K, with consecutive Akt activation. Finally, the knock-down of either Stat5 or Akt activity resulted in growth inhibition of neoplastic Kit D816V(+) MCs. These data suggest that a downstream Stat5-PI3K-Akt signaling cascade is essential for Kit D816V-mediated growth and survival of neoplastic MCs.

引用

页码：2463 / 2473

页数：11

共 50 条

[41] FLJ10540-elicited cell transformation is through the activation of PI3-kinase/AKT pathway [J].

C-H Chen ;

P-J Lu ;

Y-C Chen ;

S-L Fu ;

K-J Wu ;

A-P Tsou ;

Y-C G Lee ;

T-C E Lin ;

S-L Hsu ;

W-J Lin ;

C-Y F Huang ;

C-K Chou .

Oncogene, 2007, 26 :4272-4283

[42] FLJ10540-elicited cell transformation is through the activation of PI3-kinase/AKT pathway [J].

Chen, C-H ;

Lu, P-J ;

Chen, Y-C ;

Fu, S-L ;

Wu, K-J ;

Tsou, A-P ;

Lee, Y-C G. ;

Lin, T-C E. ;

Hsu, S-L ;

Lin, W-J ;

Huang, C-Y F. ;

Chou, C-K .

ONCOGENE, 2007, 26 (29) :4272-4283

[43] Stem cell factor synergistically enhances thrombopoietin-induced STAT5 signaling in megakaryocyte progenitors through JAK2 and Src kinase [J].

Drayer, AL ;

Boer, AK ;

Los, EL ;

Esselink, MT ;

Vellenga, E .

STEM CELLS, 2005, 23 (02) :240-251

[44] Suppressor of cytokine signaling 7 inhibits prolactin, growth hormone, and leptin signaling by interacting with STAT5 or STAT3 and attenuating their nuclear translocation [J].

Martens, N ;

Uzan, G ;

Wery, M ;

Hooghe, R ;

Hooghe-Peters, EL ;

Gertler, A .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (14) :13817-13823

[45] Leukemia inhibitory factor enhances mast cell growth in a mast cell/fibroblast co-culture system through Stat3 signaling pathway of fibroblasts [J].

Hiragun, T ;

Morita, E ;

Mihara, S ;

Tanaka, T ;

Gyotoku, E ;

Kameyoshi, Y ;

Yamamoto, S .

FEBS LETTERS, 2000, 487 (02) :219-223

[46] The Secretome of Endothelial Progenitor Cells Promotes Brain Endothelial Cell Activity through PI3-Kinase and MAP-Kinase [J].

Di Santo, Stefano ;

Seiler, Stefanie ;

Fuchs, Anna-Lena ;

Staudigl, Jennifer ;

Widmer, Hans Rudolf .

PLOS ONE, 2014, 9 (04)

[47] Extracellular mechanical cues drive vinculin mediated PI3-kinase signaling to enhance cell invasion in 3D. [J].

Rubashkin, M. ;

Cassereau, L. ;

Bainer, R. ;

DuFort, C. ;

Yui, Y. ;

Ou, G. ;

Paszek, M. J. ;

Davidson, M. W. ;

Chen, Y. ;

Weaver, V. M. .

MOLECULAR BIOLOGY OF THE CELL, 2014, 25

[48] Differential effects of STAT5 and PI3K/AKT signaling on effector and memory CD8 T-cell survival [J].

Hand, Timothy W. ;

Cui, Weiguo ;

Jung, Yong Woo ;

Sefik, Esen ;

Joshi, Nikhil S. ;

Chandele, Anmol ;

Liu, Ying ;

Kaech, Susan M. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (38) :16601-16606

[49] Competitive signaling between STAT5 and PI3K of the IL-7R modulates T cell development and homeostasis in vivo [J].

Cui, G. ;

Shimba, A. ;

Tani-ichi, S. ;

Hara, T. ;

Ikuta, K. .

EUROPEAN JOURNAL OF IMMUNOLOGY, 2016, 46 :338-338

[50] PI3 kinase plays important role in c-Kit/V560D mediated oncogenic signaling [J].

Sun, Jianmin .

CANCER RESEARCH, 2015, 75

← 1 2 3 4 5 →