Dataset Information

An oncogenic role for alternative NF-?B signaling in DLBCL revealed upon deregulated BCL6 expression.

ABSTRACT: Diffuse large B cell lymphoma (DLBCL) is a complex disease comprising diverse subtypes and genetic profiles. Possibly because of the prevalence of genetic alterations activating canonical NF-?B activity, a role for oncogenic lesions that activate the alternative NF-?B pathway in DLBCL has remained elusive. Here, we show that deletion/mutation of TRAF3, a negative regulator of the alternative NF-?B pathway, occurs in ?15% of DLBCLs and that it often coexists with BCL6 translocation, which prevents terminal B cell differentiation. Accordingly, in a mouse model constitutive activation of the alternative NF-?B pathway cooperates with BCL6 deregulation in DLBCL development. This work demonstrates a key oncogenic role for the alternative NF-?B pathway in DLBCL development.

SUBMITTER: Zhang B

PROVIDER: S-EPMC4426003 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

An oncogenic role for alternative NF-κB signaling in DLBCL revealed upon deregulated BCL6 expression.

Zhang Baochun B Calado Dinis Pedro DP Wang Zhe Z Fröhler Sebastian S Köchert Karl K Qian Yu Y Koralov Sergei B SB Schmidt-Supprian Marc M Sasaki Yoshiteru Y Unitt Christine C Rodig Scott S Chen Wei W Dalla-Favera Riccardo R Alt Frederick W FW Pasqualucci Laura L Rajewsky Klaus K

Cell reports 20150423 5

Diffuse large B cell lymphoma (DLBCL) is a complex disease comprising diverse subtypes and genetic profiles. Possibly because of the prevalence of genetic alterations activating canonical NF-κB activity, a role for oncogenic lesions that activate the alternative NF-κB pathway in DLBCL has remained elusive. Here, we show that deletion/mutation of TRAF3, a negative regulator of the alternative NF-κB pathway, occurs in ∼15% of DLBCLs and that it often coexists with BCL6 translocation, which prevent ...[more]

PMID: 25921526

Similar Datasets

Project description:RationaleCD13 is a new marker for liver cancer stem cells (CSCs) that contributes to sorafenib resistance in hepatocellular carcinoma (HCC). However, the underlying mechanism of CD13 in HCC sorafenib resistance remains enigmatic.MethodsThe expression of CD13 in HCC cell lines and tissues was assayed by RT-PCR, western-blot, and immunohistochemistry staining. Athymic BALB/c nu/nu mice model was used to study the in vivo functions of CD13. Clinical significance of CD13 was evaluated by Kaplan-Meier methods. Cellular proliferation rate was evaluated by cell counting kit-8 cell proliferation assay and colony formation assay. Tunel assay was used to detect cell death ratio. Transwell assay was used to evaluate the motility of cells. Immunoprecipitation (IP), liquid chromatography-mass spectrometry (LC-MS)/MS, and co-IP were applied to investigate potential protein interactions of CD13.ResultsIn this research, we found that CD13 expression was higher in metastatic HCC samples, and its overexpression was predicted worse prognosis for patients after surgical resection. Functionally, CD13 promoted HCC proliferation, invasion, cell cycle progression as well as sorafenib resistance. Mechanistically, CD13 interacted with histone deacetylase5 (HDAC5) to promote its protein stability, thus resulting in HDAC5-mediated lysine-specific demethylase 1 (LSD1) deacetylation and protein stabilization. Consequently, LSD1 decreased the NF-κB catalytic unit p65 methylation that led to p65 protein stability. A CD13 inhibitor ubenimex in combination with sorafenib, suppressed the tumor growth and attenuated the resistance of HCC cells toward sorafenib in patient-derived xenograft models.ConclusionsCD13 promotes HCC progression and induces sorafenib resistance, mainly via interacting with HDAC5 to prevent the degradation of p65 and activate NF-kB signaling pathway. CD13 is a prognostic indicator for HCC patients underwent curative resection as well as a predictor of response to treatment with sorafenib. Our study establishes the new therapeutic potential of targeting CD13-HDAC5-LSD1-NF-κB in HCC.

Dataset Information

An oncogenic role for alternative NF-?B signaling in DLBCL revealed upon deregulated BCL6 expression.

Publications

An oncogenic role for alternative NF-κB signaling in DLBCL revealed upon deregulated BCL6 expression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets