Essential role of MALT1 protease activity in activated B cell-like diffuse large B-cell lymphoma.
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Essential role of MALT1 protease activity in activated B cell-like diffuse large B-cell lymphoma. / Hailfinger, Stephan; Lenz, Georg; Ngo, Vu; Posvitz-Fejfar, Anita; Rebeaud, Fabien; Montserrat, Guzzardi; Murga-Penas, Eva-Maria; Dierlamm, Judith; Chan, Wing C; Staudt, Louis M; Thome, Margot.
In: P NATL ACAD SCI USA, Vol. 106, No. 47, 47, 2009, p. 19946-19951.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Essential role of MALT1 protease activity in activated B cell-like diffuse large B-cell lymphoma.
AU - Hailfinger, Stephan
AU - Lenz, Georg
AU - Ngo, Vu
AU - Posvitz-Fejfar, Anita
AU - Rebeaud, Fabien
AU - Montserrat, Guzzardi
AU - Murga-Penas, Eva-Maria
AU - Dierlamm, Judith
AU - Chan, Wing C
AU - Staudt, Louis M
AU - Thome, Margot
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 106
SP - 19946
EP - 19951
JO - P NATL ACAD SCI USA
JF - P NATL ACAD SCI USA
SN - 0027-8424
IS - 47
M1 - 47
ER -
