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

被引：95

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

[21] Regulation of Stat5 by FAK and PAK1 in Oncogenic FLT3-and KIT-Driven Leukemogenesis
Chatterjee, Anindya
Ghosh, Joydeep
Ramdas, Baskar
Mali, Raghuveer Singh
Martin, Holly
Kobayashi, Michihiro
Vemula, Sasidhar
Canela, Victor H.
Waskow, Emily R.
Visconte, Valeria
Tiu, Ramon V.
Smith, Catherine C.
Shah, Neil
Bunting, Kevin D.
Boswell, H. Scott
Liu, Yan
Chan, Rebecca J.
Kapur, Reuben
CELL REPORTS, 2014, 9 (04): : 1333 - 1348
[22] Detection of activated STAT5 in neoplastic mast cells in patients with systemic mastocytosis: Role of c-kit D816V
Sonneck, K
Mayerhofer, M
Gleixner, KV
Kerenyi, M
Krauth, MT
Fritz, R
Sillaber, C
Moriggl, R
Valent, P
BLOOD, 2005, 106 (11) : 981A - 981A
[23] STAT3/STAT5 BALANCE AS A BIOMARKER IN RA: CTLA4-IG AND T CELL DIFFERENTIATION THROUGH STAT SIGNALING
Alivernini, Stefano
Tolusso, Barbara
Fedele, Anna Laura
Di Mario, Clara
Petricca, Luca
Gigante, Maria Rita
Ferraccioli, Gianfranco
Gremese, Elisa
ANNALS OF THE RHEUMATIC DISEASES, 2019, 78 : 1100 - 1100
[24] Down-regulation of the PI3-kinase/Akt pathway by ERK MAP kinase in growth factor signaling
Hayashi, Hideko
Tsuchiya, Yoshiki
Nakayama, Kei
Satoh, Takayuki
Nishida, Eisuke
GENES TO CELLS, 2008, 13 (09) : 941 - 947
[25] PDGFRβ promotes oncogenic progression via STAT3/STAT5 hyperactivation in anaplastic large cell lymphoma
I. Garces de los Fayos Alonso
L. Zujo
I. Wiest
P. Kodajova
G. Timelthaler
S. Edtmayer
M. Zrimšek
S. Kollmann
C. Giordano
M. Kothmayer
H. A. Neubauer
S. Dey
M. Schlederer
B. S. Schmalzbauer
T. Limberger
C. Probst
O. Pusch
S. Högler
S. Tangermann
O. Merkel
A. I. Schiefer
C. Kornauth
N. Prutsch
M. Zimmerman
B. Abraham
J. Anagnostopoulos
L. Quintanilla-Martinez
S. Mathas
P. Wolf
D. Stoiber
P. B. Staber
G. Egger
W. Klapper
W. Woessmann
T. A. Look
P. Gunning
S. D. Turner
R. Moriggl
S. Lagger
L. Kenner
Molecular Cancer, 21
[26] PDGFRβ promotes oncogenic progression via STAT3/STAT5 hyperactivation in anaplastic large cell lymphoma
Alonso, I. Garces de los Fayos
Zujo, L.
Wiest, I
Kodajova, P.
Timelthaler, G.
Edtmayer, S.
Zrimsek, M.
Kollmann, S.
Giordano, C.
Kothmayer, M.
Neubauer, H. A.
Dey, S.
Schlederer, M.
Schmalzbauer, B. S.
Limberger, T.
Probst, C.
Pusch, O.
Hogler, S.
Tangermann, S.
Merkel, O.
Schiefer, A., I
Kornauth, C.
Prutsch, N.
Zimmerman, M.
Abraham, B.
Anagnostopoulos, J.
Quintanilla-Martinez, L.
Mathas, S.
Wolf, P.
Stoiber, D.
Staber, P. B.
Egger, G.
Klapper, W.
Woessmann, W.
Look, T. A.
Gunning, P.
Turner, S. D.
Moriggl, R.
Lagger, S.
Kenner, L.
MOLECULAR CANCER, 2022, 21 (01)
[27] The receptor tyrosine kinase Kit signaling through phosphatidylinositol (PI) 3-kinase stimulates mouse Leydig cell steroidogenesis.
Rothschild, G
Sottas, CM
Kissel, H
Hardy, MP
Besmer, P
BIOLOGY OF REPRODUCTION, 2001, 64 : 210 - 210
[28] Interleukin-5 suppresses Vascular Endothelial Growth Factor -induced angiogenesis through STAT5 signaling
Bucher, Felicitas
Lee, Jungho
Shin, Sanghee
Kim, Minseok S.
Oh, Yong-Seok
Ha, Sanghoon
Zhang, Hongkai
Yea, Kyungmoo
CYTOKINE, 2018, 110 : 397 - 403
[29] Endomembrane HRas controls the PI3 kinase/Akt/eNOS signaling cascade in VEGF induced endothelial cell migration
Haeussler, Dagmar
Burgoyne, Joseph R.
Hou, Xiuyun
Pimental, David R.
Cohen, Richard A.
Bachschmid, Markus M.
FASEB JOURNAL, 2013, 27
[30] Endomembrane HRas Controls the PI3 Kinase/Akt/eNOS Signaling Cascade in VEGF Induced Endothelial Cell Migration
Haeussler, Dagmar J.
Pimentel, David R.
Hou, Xiuyun
Burgoyne, Joseph R.
Cohen, Richard A.
Bachschmid, Markus M.
FREE RADICAL BIOLOGY AND MEDICINE, 2012, 53 : S31 - S31

← 1 2 3 4 5 →