ATDC/TRIM29 Drives Invasive Bladder Cancer Formation through miRNA-Mediated and Epigenetic Mechanisms

Palmbos, Phillip L.; Wang, Lidong; Yang, Haiyan; Wang, Yin; Leflein, Jacob; Ahmet, McKenzie L.; Wilkinson, John E.; Kumar‐Sinha, Chandan; Ney, Gina M.; Tomlins, Scott A.; Daignault, Stephanie; Kunju, Lakshmi P.; Wu, Xue-Ru; Lotan, Yair; Liebert, Monica; Ljungman, Mats; Simeone, Diane M.

doi:10.1158/0008-5472.can-15-0603

Cited by 59 publications

(61 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further studies have demonstrated that NEMO is also essential for virus-induced activation of IRF3 and IRF7 by recruiting TBK1 and IKKε to the RLR-MAVS complex 41 , which suggests that NEMO is a critical adaptor in both NF-κB signaling and IRF signaling. Published evidence indicates that TRIM29 might have an important role in DNA repair 42 and oncogenesis 43 , which suggests that TRIM29 might have additional functions beyond the regulation of innate immunity. Structurally, TRIM29 belongs to the large TRIM family of E3 ubiquitin ligases, but it lacks a typical RING domain.…”

Section: Discussionmentioning

confidence: 99%

Identification of a role for TRIM29 in the control of innate immunity in the respiratory tract

Weng²,

et al. 2016

View full text Add to dashboard Cite

The respiratory tract is heavily populated with innate immune cells, but the mechanisms that control such cells are poorly defined. Here we found that the E3 ubiquitin ligase TRIM29 was a selective regulator of the activation of alveolar macrophages, the expression of type I interferons and the production of proinflammatory cytokines in the lungs. We found that deletion of TRIM29 enhanced macrophage production of type I interferons and protected mice from infection with influenza virus, while challenge of Trim29−/− mice with Haemophilus influenzae resulted in lethal lung inflammation due to massive production of proinflammatory cytokines by macrophages. Mechanistically, we demonstrated that TRIM29 inhibited interferon-regulatory factors and signaling via the transcription factor NF-κB by degrading the adaptor NEMO and that TRIM29 directly bound NEMO and subsequently induced its ubiquitination and proteolytic degradation. These data identify TRIM29 as a key negative regulator of alveolar macrophages and might have important clinical implications for local immunity and immunopathology.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of a role for TRIM29 in the control of innate immunity in the respiratory tract

Weng²,

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Palmbos et al reported that TRIM29 overexpression in invasive bladder cancer was associated with poor prognosis (Palmbos et al, 2015). In HCC, the expression of several TRIM proteins, such as TRIM44 and TRIM26, was able to predict the overall survival of patients Zhu et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

TRIM65 triggers β-catenin signaling via ubiquitylation of Axin1 to promote hepatocellular carcinoma

Yang

Zhang

Qing

et al. 2017

Journal of Cell Science

View full text Add to dashboard Cite

Deregulation of ubiquitin ligases contributes to the malignant progression of human cancers. Tripartite motif-containing protein 65 (TRIM65) is an E3 ubiquitin ligase and has been implicated in human diseases, but its role and clinical significance in hepatocellular carcinoma (HCC) remain unknown. Here, we showed that TRIM65 expression was increased in HCC tissues and associated with poor outcome in two independent cohorts containing 888 patients. In vitro and in vivo data demonstrated that overexpression of TRIM65 promoted cell growth and tumor metastasis, whereas knockdown of TRIM65 resulted in opposite phenotypes. Further studies revealed that TRIM65 exerted oncogenic activities via ubiquitylation of Axin1 to activate the β-catenin signaling pathway. TRIM65 directly bound to Axin1 and accelerated its degradation through ubiquitylation. Furthermore, HMGA1 was identified as an upstream regulator of TRIM65 in HCC cells. In clinical samples, TRIM65 expression was positively correlated with the expression of HMGA1 and nuclear β-catenin. Collectively, our data indicate that TRIM65 functions as an oncogene in HCC. The newly identified HMGA1/TRIM65/β-catenin axis serves as a promising prognostic factor and therapeutic target.

show abstract

“…The TRIM2 function in cancers has been associated with its E3 ubiquitin ligase activity towards BIM/BCL2L11, its pro-apoptotic substrate 46, 47 . Pro-tumorigenic activities of TRIM29 appear to be mediated via multiple mechanisms as its overexpression in cancers was linked with suppression of p53, PTEN, and promotion of radioresistance and other stem cell properties 48–51 . Other potentially useful therapeutic targets within the PROM1 signature were MPZL2/EVA1, which has been recently linked to maintenance of glioblastoma stem cells through activation of non-canonical NFkB pathway 52 , and KCNN4 that encodes potassium channel KCa3.1 involved in regulation of motility in glioblastoma stem cells 53 .…”

Section: Resultsmentioning

confidence: 99%

Expression Profiling of Clinical Specimens Supports the Existence of Neural Progenitor-Like Stem Cells in Basal Breast Cancers

Panaccione

Guo

Yarbrough

et al. 2017

Clinical Breast Cancer

View full text Add to dashboard Cite

To facilitate development of CSC-targeting therapies, we analyzed publicly available breast cancer datasets to identify genes co-expressed with SOX10, a neural crest marker, and PROM1/CD133, a common CSC marker. The conserved SOX10/PROM1 gene signature that we characterized supports the existence in basal breast cancers of SOX10+/CD133+ cells with neural stem-like features exposing clinically relevant CSC markers and signaling networks. Background We previously characterized in salivary adenoid cystic carcinoma (ACC) a novel population of CSC marked by co-expression of two stemness genes, SOX10 and CD133. We also reported that in ACC and basal-like breast carcinoma (BBC), a triple-negative breast cancer subtype, expression of SOX10 similarly demarcates a highly conserved gene signature enriched with neural stem cell genes. Based on these findings, we hypothesized that BBC may be likewise driven by SOX10+/CD133+ cells with neural stem cell properties. Methods To validate our hypothesis on clinical data, we used a novel approach to meta-analysis that merges gene expression data from independent breast cancer studies and ranks genes by statistical significance of their co-expression with the gene of interest. Genes that showed strong association with both CD133/PROM1 and SOX10 were validated across different platforms and datasets and analyzed for enrichment with genes involved in neurogenesis. Results We identified in clinical breast cancer datasets a highly conserved SOX10/PROM1 gene signature that contains neural stem cell markers common for Schwann cells, ACC, BBC, and melanoma. Identification of TRIM2, TRIM29, MPZL2, KCNN4, and VTCN1/B7-H4 within this signature provides insight into molecular mechanisms of CSC maintenance. Conclusion Our results suggest that BBC is driven by SOX10+/CD133+ cells that express NSC-specific markers and share molecular similarities with CSC of neural crest origin. Our study provides clinically relevant information on possible drivers of these cells that may facilitate development of CSC-targeting therapies against this cancer distinguished with poor prognosis and resistance to conventional therapies.

show abstract

ATDC/TRIM29 Drives Invasive Bladder Cancer Formation through miRNA-Mediated and Epigenetic Mechanisms

Cited by 59 publications

References 43 publications

Identification of a role for TRIM29 in the control of innate immunity in the respiratory tract

Identification of a role for TRIM29 in the control of innate immunity in the respiratory tract

TRIM65 triggers β-catenin signaling via ubiquitylation of Axin1 to promote hepatocellular carcinoma

Expression Profiling of Clinical Specimens Supports the Existence of Neural Progenitor-Like Stem Cells in Basal Breast Cancers

Contact Info

Product

Resources

About