The many faces and functions of β-catenin

Valenta, Tomáš; Hausmann, George; Basler, Konrad

doi:10.1038/emboj.2012.150

Cited by 1,391 publications

(1,335 citation statements)

References 259 publications

Supporting

Mentioning

1,297

Contrasting

Unclassified

Order By: Relevance

“…This process is critical for numerous cellular processes, such as normal cell renewal and regeneration, regulation of tissue homeostasis and differentiation, maintaining normal cellular architecture, and controlling cell-to-cell adhesion [14]. Mutations in the APC gene cause an increase in b-catenin expression, which activates oncogenes and leads to a variety of neoplasms and cancers [6,15].…”

Section: Discussionmentioning

confidence: 99%

Desmoplastic Fibroma of the Mandible: A Series of Three Cases and Review of Literature

Woods

Cohen

Islam

et al. 2014

Head and Neck Pathol

View full text Add to dashboard Cite

The desmoplastic fibroma (DF) is a rare, fibroblastic lesion of bone that histologically resembles the desmoid tumor of soft tissue. Although classified as benign, it frequently demonstrates aggressive behavior, often causing tooth mobility, extensive bone destruction, and has a moderate to high recurrence rate. We present three cases of DF in the mandible: the first in a 13 year old female involving the mandibular body in the region of teeth #s 27-#28, the second in a 57 year old female with a lesion apical to tooth #30, and the third in a 20-year-old female involving the left posterior mandible. Clinical, histologic, immunohistochemical (IHC) and radiographic features of this rare neoplasm are discussed. The challenges encountered in establishing an accurate diagnosis due to significant microscopic overlap with other spindle cell lesions are also detailed. Additionally, the findings of IHC stains including vimentin, smooth muscle actin, S-100 protein, bcatenin, HHF-35 and proliferation marker, Ki-67 on 3 cases are reported. The potential for misdiagnosis is high, especially in early lesions, since immunohistochemistry has been reported in literature to be inconsistent when differentiating DFs from other spindle cell lesions. A comparative review of DF and similar entities in the jaws with current considerations in treatment and prognosis is presented.

show abstract

Section: Discussionmentioning

confidence: 99%

Desmoplastic Fibroma of the Mandible: A Series of Three Cases and Review of Literature

Woods

Cohen

Islam

et al. 2014

Head and Neck Pathol

View full text Add to dashboard Cite

show abstract

“…During canonical signaling, secreted Wnt ligands bind to their Frizzled receptors to induce cytoplasmic accumulation and nuclear translocation of β-catenin (Clevers and Nusse, 2012;Mikels and Nusse, 2006), which is the key intracellular component of the transduction cascade. In the nucleus, β-catenin binds to the TCF/LEF transcription factors, triggering changes in chromatin conformation and gene transcription (Komiya and Habas, 2008;Valenta et al, 2012). Thus, β-catenin acts as a master regulatory gene, responsible for the control of multiple processes.…”

Section: Introductionmentioning

confidence: 99%

Localization of planarian β-CATENIN-1 reveals multiple roles during anterior-posterior regeneration and organogenesis

2016

View full text Add to dashboard Cite

The β-catenin-dependent Wnt pathway exerts multiple contextdependent roles in embryonic and adult tissues. In planarians, β-catenin-1 is thought to specify posterior identities through the generation of an anteroposterior gradient. However, the existence of such a gradient has not been directly demonstrated. Here, we use a specific polyclonal antibody to demonstrate that nuclear β-CATENIN-1 exists as an anteroposterior gradient from the pre-pharyngeal region to the tail of the planarian Schmidtea polychroa. High levels in the posterior region steadily decrease towards the pre-pharyngeal region but then increase again in the head region. During regeneration, β-CATENIN-1 is nuclearized in both anterior and posterior blastemas, but the canonical WNT1 ligand only influences posterior nuclearization. Additionally, β-catenin-1 is required for proper anterior morphogenesis, consistent with the high levels of nuclear β-CATENIN-1 observed in this region. We further demonstrate that β-CATENIN-1 is abundant in developing and differentiated organs, and is particularly required for the specification of the germline. Altogether, our findings provide the first direct evidence of an anteroposterior nuclear β-CATENIN-1 gradient in adult planarians and uncover novel, context-dependent roles for β-catenin-1 during anterior regeneration and organogenesis.

show abstract

“…2 Several cytoplasmic tyrosine kinases and growth factor-activated receptor tyrosine kinases (RTK) phosphorylate b-catenin, thus promoting a migratory phenotype. [3][4][5] Dynamic regulation by tyrosine phosphatases counteracts b-catenin phosphorylation. 1,2 In addition, b-catenin is a transducer of Wnt signaling that plays central roles in development, the balance of cell proliferation/differentiation and cancer.…”

Section: Introductionmentioning

confidence: 99%

“…1,2 In addition, b-catenin is a transducer of Wnt signaling that plays central roles in development, the balance of cell proliferation/differentiation and cancer. 5,6 In the absence of Wnt ligands, b-catenin assembles into a complex containing Glycogen Synthase Kinase (GSK)-3b and additional Wnt pathway components. The S/T kinase GSK-3b phosphorylates b-catenin at its Nterminal domain, which favors its proteasomal degradation.…”

Section: Introductionmentioning

confidence: 99%

Nuclear phosphorylated Y142 β-catenin accumulates in astrocytomas and glioblastomas and regulates cell invasion

et al. 2015

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM) is a fast growing brain tumor characterized by extensive infiltration into the surrounding tissue and one of the most aggressive cancers. GBM is the most common glioma (originating from glialderived cells) that either evolves from a low grade astrocytoma or appears de novo. Wnt/b-catenin and Hepatocyte Growth Factor (HGF)/c-Met signaling are hyperactive in human gliomas, where they regulate cell proliferation, migration and stem cell behavior. We previously demonstrated that b-catenin is phosphorylated at Y142 by recombinant c-Met kinase and downstream of HGF signaling in neurons. Here we studied phosphoY142 (PY142) b-catenin and dephospho S/T b-catenin (a classical Wnt transducer) in glioma biopsies, GBM cell lines and biopsyderived glioma cell cultures. We found that PY142 b-catenin mainly localizes in the nucleus and signals through transcriptional activation in GBM cells. Tissue microarray analysis confirmed strong nuclear PY142 b-catenin immunostaining in astrocytoma and GBM biopsies. By contrast, active b-catenin showed nuclear localization only in GBM samples. Western blot analysis of tumor biopsies further indicated that PY142 and active b-catenin accumulate independently, correlating with the expression of Snail/Slug (an epithelial-mesenchymal transition marker) and Cyclin-D1 (a regulator of cell cycle progression), respectively, in high grade astrocytomas and GBMs. Moreover, GBM cells stimulated with HGF showed increasing levels of PY142 b-catenin and Snail/Slug. Importantly, the expression of mutant Y142F b-catenin decreased cell detachment and invasion induced by HGF in GBM cell lines and biopsy-derived cell cultures. Our results identify PY142 b-catenin as a nuclear b-catenin signaling form that downregulates adhesion and promotes GBM cell invasion.

show abstract

The many faces and functions of β-catenin

Cited by 1,391 publications

References 259 publications

Desmoplastic Fibroma of the Mandible: A Series of Three Cases and Review of Literature

Desmoplastic Fibroma of the Mandible: A Series of Three Cases and Review of Literature

Localization of planarian β-CATENIN-1 reveals multiple roles during anterior-posterior regeneration and organogenesis

Nuclear phosphorylated Y142 β-catenin accumulates in astrocytomas and glioblastomas and regulates cell invasion

Contact Info

Product

Resources

About