An Anti-Apoptotic Role for Galectin-3 in Diffuse Large B-Cell Lymphomas

Hoyer, Katrina K.; Pang, Mabel; Gui, Dorina; Shintaku, I. Peter; Kuwabara, Ichiro; Liu, Fu‐Tong; Said, Jonathan; Baum, Linda G.; Teitell, Michael A.

doi:10.1016/s0002-9440(10)63177-x

Cited by 102 publications

(91 citation statements)

References 65 publications

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“…The expression of an N-terminal truncated Gal3 has previously been shown to have a dominant-negative effect. 41 We also found that tumor growth could not be rescued by either wild-type or mutated Gal3 in c-Abl/Arg knockdown tumor cells, suggesting that the oncogenicity of Gal3 is dependent on the activity of c-Abl or Arg.…”

Section: Discussionmentioning

confidence: 72%

c-Abl and Arg tyrosine kinases regulate lysosomal degradation of the oncoprotein Galectin-3

Li¹,

Ma²,

Wang

et al. 2010

Cell Death Differ

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Galectin-3 (Gal3) has important roles in tumor transformation and metastasis. This study shows that c-Abl and Abl-related gene (Arg) associate with and phosphorylate Gal3. The SH (Src homology)3 domains of c-Abl/Arg bind to a P 80 GPPSGP motif of Gal3, and Tyr79 and Tyr118 are the major tyrosine phosphorylation sites. A consequence of this interaction and phosphorylation is the significant impairment of chaperone-mediated autophagy of Gal3. Cells expressing Gal3 and treated with the c-Abl/Arg inhibitor STI571, Gal3-depleted cells, and Gal3-depleted cells expressing Gal3 phosphorylation mutants all display an increased sensitivity to apoptosis-inducing agents. In addition, tumor cells expressing the phosphorylation mutants show impaired tumorigenicity. These results partially explain the antiapoptotic effect of Abl and Arg. As tumors frequently overexpress Gal3, a c-Abl/Arg-specific inhibitor may potentially be applied along with other antitumor drugs to target the lysosomal degradation of Gal3 in tumor therapy.

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Section: Discussionmentioning

confidence: 72%

c-Abl and Arg tyrosine kinases regulate lysosomal degradation of the oncoprotein Galectin-3

Li¹,

Ma²,

Wang

et al. 2010

Cell Death Differ

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“…19 We found that intracellular LGALS3 was associated with poor prognosis in classical Hodgkin's lymphoma patients, in agreement with previous studies of LGALS3 in solid tumors and other lymphomas. 7,8,18 In contrast to LGALS3, BCL2 expression was not associated with overall survival or event-free survival. Although LGALS3 is not a member of the BCL2 gene family, it shares several significant structural properties with BCL2.…”

Section: Discussionmentioning

confidence: 95%

“…18 Likewise, Burkitt lymphoma cells transfected with a LGALS3-expressing plasmid show increased resistance to anti-Fas-induced cell death. 8 On the other hand, secreted extracellular LGALS3 molecules induce T-cell apoptosis, thereby having an important role in the immune escape during tumor progression, through induction of apoptosis of cancer-infiltrating T-cells. 19 We found that intracellular LGALS3 was associated with poor prognosis in classical Hodgkin's lymphoma patients, in agreement with previous studies of LGALS3 in solid tumors and other lymphomas.…”

Section: Discussionmentioning

confidence: 99%

“…6 Moreover, LGALS3 has an important role in angiogenesis and metastases in several malignancies, including B-cell lymphomas. [7][8][9] B-cell lymphoma-2 (BCL2) protein inhibits apoptosis by preventing cytochrome release from mitochondria, thus blocking oxidative cell destruction. Over-expression of BCL2 has been found in some solid malignancies and malignant lymphomas including classical Hodgkin's lymphoma.…”

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confidence: 99%

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LGALS3 as a prognostic factor for classical Hodgkin's lymphoma

et al. 2014

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LGALS3, a member of the lectin family, has an important role in tumor progression through inhibition of apoptosis.LGALS3 shares several significant structural properties with BCL2. In this study, we examined the prognostic significance of LGALS3 and BCL2 in uniformly treated classical Hodgkin's lymphoma. Diagnostic tissues from 110 patients with uniformly treated classical Hodgkin's lymphoma were evaluated retrospectively by immunohistochemical analysis of LGALS3 and BCL2 expression. The median follow-up time was 6.2 years (range, 0.2-17.3 years). Twenty-seven patients (25%) expressed LGALS3 protein in Hodgkin/Reed-Sternberg cells, which was associated with poor overall survival and event-free survival (P ¼ 0.007 and Po0.001). Fifteen patients (14%) expressed BCL2 protein in Hodgkin/Reed-Sternberg cells, which was not associated with overall survival and event-free survival (P ¼ 0.928 and P ¼ 0.900).There was no correlation between LGALS3 and BCL2 expression (P ¼ 0.193). Multivariate analysis identified LGALS3 protein as an independent prognostic factor for event-free survival (P ¼ 0.007). Subgroup analysis according to the Ann Arbor stage of classical Hodgkin's lymphoma showed that LGALS3 protein expression had a prognostic value in limited-stage classical Hodgkin's lymphoma (Po0.001). The results of this study suggest that LGALS3 is an independent prognostic factor in classical Hodgkin's lymphoma, and may allow the identification of a subgroup of patients with limited-stage classical Hodgkin's lymphoma who require more intensive therapy. Modern Pathology (2014) 27, 1338-1344; doi:10.1038/modpathol.2014.38; published online 7 March 2014 Keywords: BCL2; Hodgkin's lymphoma; LGALS3; prognosis Classical Hodgkin's lymphoma is a highly curable lymphoid malignancy. 1 However, despite important treatment advances, a minority of patients do not respond to therapy or relapse after optimal initial therapeutic strategy, and may require adapted firstline treatment. 2 While the International Prognostic Score is useful in clinical practice, it does not fully reflect the biological behavior of classical Hodgkin's lymphoma. 3 Galectins, a family of mammalian b-galactosidebinding lectin molecules, are implicated in inflammation and tumor progression. 4 LGALS3 is expressed in lymphoma and myeloma cells, 5,6 and has both pro-apoptotic and antiapoptotic functions. 7 A recent study demonstrated that high expression of LGALS3 protein in diffuse large B-cell lymphoma cells was associated with resistance to apoptosis. 6 Moreover, LGALS3 has an important role in angiogenesis and metastases in several malignancies, including B-cell lymphomas. [7][8][9] B-cell lymphoma-2 (BCL2) protein inhibits apoptosis by preventing cytochrome release from mitochondria, thus blocking oxidative cell destruction. Over-expression of BCL2 has been found in some solid malignancies and malignant lymphomas including classical Hodgkin's lymphoma. [10][11][12][13] The BCL2 family of antiapoptotic proteins contribute to the survival of Hodgkin/Reed-Sternberg cell...

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“…Известно, что интрацеллюлярный (цитоплазматиче-ский) галектин-3 -ингибитор апоптоза [7]. Вслед за апоптотическими стимулами цитоплазматический галектин-3 взаимодействует с Са 2+ -зависимым и фосфо-липид-связывающим белком -синексином.…”

Section: галектин-3 -биомаркер фиброза у пациентов с метаболическим сunclassified

Galectin-3 — Biomarker of Fibrosis in Patients With Metabolic Syndrome

Драпкина¹,

Deeva²

2015

Ross. kardiol. ž.

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An Anti-Apoptotic Role for Galectin-3 in Diffuse Large B-Cell Lymphomas

Cited by 102 publications

References 65 publications

c-Abl and Arg tyrosine kinases regulate lysosomal degradation of the oncoprotein Galectin-3

c-Abl and Arg tyrosine kinases regulate lysosomal degradation of the oncoprotein Galectin-3

LGALS3 as a prognostic factor for classical Hodgkin's lymphoma

Galectin-3 — Biomarker of Fibrosis in Patients With Metabolic Syndrome

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