Essential role of MALT1 protease activity in activated B cell-like diffuse large B-cell lymphoma

被引：178

作者：

Hailfinger, Stephan ^{[1
]}

Lenz, Georg ^{[2
]}

Ngo, Vu ^{[2
]}

Posvitz-Fejfar, Anita ^{[1
]}

Rebeaud, Fabien ^{[1
]}

Guzzardi, Montserrat ^{[1
]}

Penas, Eva-Maria Murga ^{[3
]}

Dierlamm, Judith ^{[3
]}

Chan, Wing C. ^{[4
]}

Staudt, Louis M. ^{[2
]}

Thome, Margot ^{[1
]}

机构：

[1] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland

[2] NCI, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA

[3] Univ Med Ctr Hamburg Eppendorf, Dept Hematol & Oncol, D-20246 Hamburg, Germany

[4] Univ Nebraska, Dept Pathol & Microbiol, Omaha, NE 68198 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 47期

基金：

美国国家卫生研究院; 瑞士国家科学基金会;

关键词：

DLBCL; NF-kB; NF-KAPPA-B; T-CELL; C-FLIP; EXPRESSION; LYMPHOCYTES; INHIBITORS; CARMA1; DIFFERENTIATION; CHEMOTHERAPY; MALIGNANCIES;

D O I：

10.1073/pnas.0907511106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

A key element for the development of suitable anti-cancer drugs is the identification of cancer-specific enzymatic activities that can be therapeutically targeted. Mucosa-associated lymphoid tissue transformation protein 1 (MALT1) is a proto-oncogene that contributes to tumorigenesis in diffuse large B-cell lymphoma (DLBCL) of the activated B-cell (ABC) subtype, the least curable subtype of DLBCL. Recent data suggest that MALT1 has proteolytic activity, but it is unknown whether this activity is relevant for tumor growth. Here we report that MALT1 is constitutively active in DLBCL lines of the ABC but not the GCB subtype. Inhibition of the MALT1 proteolytic activity led to reduced expression of growth factors and apoptosis inhibitors, and specifically affected the growth and survival of ABC DLBCL lines. These results demonstrate a key role for the proteolytic activity of MALT1 in DLBCL of the ABC subtype, and provide a rationale for the development of pharmacological inhibitors of MALT1 in DLBCL therapy.

引用

页码：19946 / 19951

页数：6

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