ON 01910.Na inhibits growth of diffuse large B-cell lymphoma by cytoplasmic sequestration of sumoylated C-MYB/TRAF6 complex

Dai, Yi; Hung, Liang‐Yi; Chen, Ruo Yu; Lai, Chin‐Feng; Chang, Kung Chao

doi:10.1016/j.trsl.2016.04.001

Cited by 14 publications

(21 citation statements)

References 47 publications

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“…The cells were cultured at 37 °C and 7% CO 2 in RPMI 1640 medium (Gibco/BRL, Grand Island, NY, USA) supplemented with 10% heat-inactivated fetal bovine serum (FBS), 4 mM of glutamine, 75 units/ml of streptomycin, and 100 units/ ml of penicillin. Cell viability was determined using the trypan blue exclusion test or MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay 18 . Transformed B-lymphoblastoid cell lines (LCLs) immortalized by Epstein-Barr virus (EBV) infection were used for comparisons 18 .…”

Section: Dlbcl Cell Lines and Ebv-transformed Lymphoblastoid Cell Linmentioning

confidence: 99%

“…Cell viability was determined using the trypan blue exclusion test or MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay 18 . Transformed B-lymphoblastoid cell lines (LCLs) immortalized by Epstein-Barr virus (EBV) infection were used for comparisons 18 .…”

Section: Dlbcl Cell Lines and Ebv-transformed Lymphoblastoid Cell Linmentioning

confidence: 99%

“…Immunofluorescent staining. Immunofluorescent staining was performed as described in a previous study 18 . Briefly, DLBCL (2 × 10 6 ) cells were cultured in 6-well plates.…”

Section: Reverse Transcriptase-polymerase Chain Reaction (Rt-pcr) Andmentioning

confidence: 99%

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Stem cell characteristics promote aggressiveness of diffuse large B-cell lymphoma

Chang

Chen

Wang

et al. 2020

Sci Rep

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Diffuse large B-cell lymphoma (DLBCL) may present initially in bone marrow, liver and spleen without any lymphadenopathy (referred to as BLS-type DLBCL), which is aggressive and frequently associated with hemophagocytic syndrome. Its tumorigenesis and molecular mechanisms warrant clarification. By gene microarray profiling with bioinformatics analysis, we found higher expression of the stem cell markers HOXA9 and NANOG, as well as BMP8B, CCR6 and S100A8 in BLS-type than conventional DLBCL. We further validated expression of these markers in a large cohort of DLBCL including BLS-type cases and found that expression of HOXA9 and NANOG correlated with inferior outcome and poor prognostic parameters. Functional studies with gene-overexpressed and gene-silenced DLBCL cell lines showed that expression of NANOG and HOXA9 promoted cell viability and inhibited apoptosis through suppression of G2 arrest in vitro and enhanced tumor formation and hepatosplenic infiltration in a tail-vein-injected mouse model. Additionally, HOXA9-transfected tumor cells showed significantly increased soft-agar clonogenic ability and tumor sphere formation. Interestingly, B cells with higher CCR6 expression revealed a higher chemotactic migration for CCL20. Taken together, our findings support the concept that tumor or precursor cells of BLS-type DLBCL are attracted by chemotaxis and home to the bone marrow, where the microenvironment promotes the expression of stem cell characteristics and aggressiveness of tumor cells.

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Section: Dlbcl Cell Lines and Ebv-transformed Lymphoblastoid Cell Linmentioning

confidence: 99%

Section: Dlbcl Cell Lines and Ebv-transformed Lymphoblastoid Cell Linmentioning

confidence: 99%

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Stem cell characteristics promote aggressiveness of diffuse large B-cell lymphoma

Chang

Chen

Wang

et al. 2020

Sci Rep

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“…B cell-specific TRAF6 −/− mice (B-TRAF6 −/− ) mice also exhibit reduced numbers of mature B cells in the BM and spleen as well as defective B1 B cell development (Table 2 ) ( 82 ). Knockdown of TRAF6 or inhibition of the TRAF6-NF-κB axis induces apoptosis and cell cycle arrest in DLBCL, and also inhibits the proliferation and bone resorption of MM ( 243 , 244 ). Interestingly, T cell-specific TRAF6 −/− mice (T-TRAF6 −/− ) mice show multiorgan inflammation due to hyperactivation of the PI3K-Akt pathway in T cells (Table 2 ) ( 83 ).…”

Section: Traf6mentioning

confidence: 99%

Genetic Alterations of TRAF Proteins in Human Cancers

et al. 2018

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The tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family of cytoplasmic adaptor proteins regulate the signal transduction pathways of a variety of receptors, including the TNF-R superfamily, Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), and cytokine receptors. TRAF-dependent signaling pathways participate in a diverse array of important cellular processes, including the survival, proliferation, differentiation, and activation of different cell types. Many of these TRAF-dependent signaling pathways have been implicated in cancer pathogenesis. Here we analyze the current evidence of genetic alterations of TRAF molecules available from The Cancer Genome Atlas (TCGA) and the Catalog of Somatic Mutations in Cancer (COSMIC) as well as the published literature, including copy number variations and mutation landscape of TRAFs in various human cancers. Such analyses reveal that both gain- and loss-of-function genetic alterations of different TRAF proteins are commonly present in a number of human cancers. These include pancreatic cancer, meningioma, breast cancer, prostate cancer, lung cancer, liver cancer, head and neck cancer, stomach cancer, colon cancer, bladder cancer, uterine cancer, melanoma, sarcoma, and B cell malignancies, among others. Furthermore, we summarize the key in vivo and in vitro evidence that demonstrates the causal roles of genetic alterations of TRAF proteins in tumorigenesis within different cell types and organs. Taken together, the information presented in this review provides a rationale for the development of therapeutic strategies to manipulate TRAF proteins or TRAF-dependent signaling pathways in different human cancers by precision medicine.

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“…Small‐molecule inhibitors of MYB are being developed, some of which show promise in preclinical experiments. For example, the multi‐kinase inhibitor Rigosertib induces selective killing of diffuse large B cell lymphoma by suppressing TRAF6 and MYB . Interestingly, TRAF6 is an adaptor protein involved in tumour development and was previously shown to be a CYLD target protein .…”

mentioning

confidence: 99%

Cutaneous cylindroma: it's all about MYB

Corda

Sala

2016

J. Pathol.

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Cutaneous cylindroma is a rare benign tumour that occasionally turns into malignant cylindrocarcinoma. The cancer can be sporadic or emerge in the context of Brooke-Spiegler syndrome (BSS), an inheritable condition characterized by mutation of the gene CYLD, encoding a tumour suppressor protein that controls the activity of the transcription factor NF-kB. Sporadic cylindromas present histological features shared with adenoid cystic carcinoma (ACC), a head and neck cancer originating from salivary or other exocrine glands. Like ACCs, sporadic cylindromas express, although at lower frequency, the aberrant fusion transcript MYB-NFIB. In a paper recently published in the Journal of Pathology, the research teams led by Neil Rajan and Goran Stenman demonstrate that CYLD-defective cyclindromas in BSS patients are negative for the MYB-NFIB fusion. Only the wild-type MYB oncoprotein is activated in the majority of these tumours. RNA interference studies in cells derived from BSS patients indicate that ablating MYB expression results in a striking reduction of cylindroma cell proliferation, suggesting that MYB plays a pivotal role in the biology of this cancer. The take-home message of the study is that activation of MYB, in its wild-type form or fusion derivatives, is a common feature of spontaneous and hereditary cylindromas, constituting a potentially actionable therapeutic target.

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ON 01910.Na inhibits growth of diffuse large B-cell lymphoma by cytoplasmic sequestration of sumoylated C-MYB/TRAF6 complex

Cited by 14 publications

References 47 publications

Stem cell characteristics promote aggressiveness of diffuse large B-cell lymphoma

Stem cell characteristics promote aggressiveness of diffuse large B-cell lymphoma

Genetic Alterations of TRAF Proteins in Human Cancers

Cutaneous cylindroma: it's all about MYB

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