Nuclear Factor of Activated T Cells (NFAT) Proteins Repress Canonical Wnt Signaling via Its Interaction with Dishevelled (Dvl) Protein and Participate in Regulating Neural Progenitor Cell Proliferation and Differentiation

Huang, Tao; Xie, Zhihui; Wang, Jiyong; Li, Meng; Jing, Naihe; Li, Lin

doi:10.1074/jbc.m111.251165

Cited by 43 publications

(37 citation statements)

References 43 publications

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“…Moreover, we found that many of these genes are putatively regulated by three transcription factors (E12, LEF1, and NFAT; Table S4), all of which are known to regulate neural progenitor cell proliferation/differentiation either through the Wnt/β-catenin signaling pathway (LEF1, NFAT) or through basic-loop-helix factors (E12) (26)(27)(28)(29).…”

Section: Resultsmentioning

confidence: 99%

Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics

Sottoriva

Spiteri

Piccirillo

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

1,525

1,304

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Glioblastoma (GB) is the most common and aggressive primary brain malignancy, with poor prognosis and a lack of effective therapeutic options. Accumulating evidence suggests that intratumor heterogeneity likely is the key to understanding treatment failure. However, the extent of intratumor heterogeneity as a result of tumor evolution is still poorly understood. To address this, we developed a unique surgical multisampling scheme to collect spatially distinct tumor fragments from 11 GB patients. We present an integrated genomic analysis that uncovers extensive intratumor heterogeneity, with most patients displaying different GB subtypes within the same tumor. Moreover, we reconstructed the phylogeny of the fragments for each patient, identifying copy number alterations in EGFR and CDKN2A/B/p14ARF as early events, and aberrations in PDGFRA and PTEN as later events during cancer progression. We also characterized the clonal organization of each tumor fragment at the singlemolecule level, detecting multiple coexisting cell lineages. Our results reveal the genome-wide architecture of intratumor variability in GB across multiple spatial scales and patient-specific patterns of cancer evolution, with consequences for treatment design.tumor progression | high grade glioma

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Section: Resultsmentioning

confidence: 99%

Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics

Sottoriva

Spiteri

Piccirillo

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

1,525

1,304

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“…Different noncanonical Wnts may have different effects in this regard. For example, Wnt5a exerts dual functions: stimulating Ca 2+ -induced NFAT nuclear localization or restricting NFAT nuclear localization via Cdc42-CK1α complex (Dejmek et al, 2006; Huang et al, 2011; Saneyoshi et al, 2002). However, Wnt11 inhibits Ca 2+ influx through restricting L-type calcium channel (LTCC) (Panáková et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Noncanonical Wnt Signaling Maintains Hematopoietic Stem Cells in the Niche

Sugimura

Venkatraman

et al. 2012

Cell

267

238

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SUMMARY Wnt signaling is involved in self-renewal and maintenance of hematopoietic stem cells (HSCs); however, the particular role of noncanonical Wnt signaling in regulating HSCs in vivo is largely unknown. Here, we show Flamingo (Fmi) and Frizzled (Fz) 8, members of noncanonical Wnt signaling, both express in and functionally maintain quiescent long-term HSCs. Fmi regulates Fz8 distribution at the interface between HSCs and N-cadherin+ osteoblasts (N-cad+OBs that enrich osteoprogenitors) in the niche. We further found that N-cad+OBs predominantly express noncanonical Wnt ligands and inhibitors of canonical Wnt signaling under homeostasis. Under stress, noncanonical Wnt signaling is attenuated and canonical Wnt signaling is enhanced in activation of HSCs. Mechanistically, noncanonical Wnt signaling mediated by Fz8 suppresses the Ca2+-NFAT- IFNγ pathway, directly or indirectly through the CDC42-CK1α complex and also antagonizes canonical Wnt signaling in HSCs. Taken together, our findings demonstrate that noncanonical Wnt signaling maintains quiescent long-term HSCs through Fmi and Fz8 interaction in the niche.

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“…We have known for over a decade now that Wnt ligands are able to induce the release of intracellular Ca 2ϩ to activate Ca 2ϩ -dependent enzymes such as phosphatase, calcineurin (Calcin), protein kinase C (PKC), and calmodulin-dependent kinase II (CamKII) (30)(31)(32) to mediate diverse effects in animal tissues. PKC and CamKII control dorsoventral patterning in embryos (32, 33) through modulation of cell adhesion, migration, and differentiation, which are regulated by the transcription factor nuclear factor of activated T cells (NFAT) (34,35). Calcineurin, on the other hand, activates nemo-like kinase (NLK) to phosphorylate TCF transcription factors and antagonize canonical WNT signaling (36).…”

Section: Figmentioning

confidence: 99%

WNT Signaling: an Emerging Mediator of Cancer Cell Metabolism?

Sherwood

2015

Molecular and Cellular Biology

129

105

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WNT signaling was discovered in tumor models and has been recognized as a regulator of cancer development and progression for over 3 decades. Recent work has highlighted a critical role for WNT signaling in the metabolic homeostasis of mammals, where its misregulation has been heavily implicated in diabetes. While the majority of WNT metabolism research has focused on nontransformed tissues, the role of WNT in cancer metabolism remains underinvestigated. Cancer is also a metabolic disease where oncogenic signaling pathways regulate energy production and macromolecular synthesis to fuel rapidly proliferating tumors. This review highlights the emerging evidence for WNT signaling in the reprogramming of cancer cell metabolism and examines the role of these signaling pathways as mediators of tumor bioenergetics.

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Nuclear Factor of Activated T Cells (NFAT) Proteins Repress Canonical Wnt Signaling via Its Interaction with Dishevelled (Dvl) Protein and Participate in Regulating Neural Progenitor Cell Proliferation and Differentiation

Cited by 43 publications

References 43 publications

Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics

Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics

Noncanonical Wnt Signaling Maintains Hematopoietic Stem Cells in the Niche

WNT Signaling: an Emerging Mediator of Cancer Cell Metabolism?

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