O2 regulates stem cells through Wnt/β-catenin signalling

Mazumdar, Jolly; O’Brien, William T.; Johnson, Randall S.; LaManna, Joseph Charles; Chávez, Juan C.; Klein, Peter S.; Simon, M. Celeste

doi:10.1038/ncb2102

Cited by 412 publications

(401 citation statements)

References 33 publications

(37 reference statements)

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“…In these studies, Hif-1␣ interacted with ␤-catenin via its NH 2 terminus and thereby inhibited the interaction of ␤-catenin with TCF4. However, the regulation of Wnt/␤-catenin signaling may be cell-and differentiation stage-specific as Hif-1 was recently reported to enhance canonical Wnt signaling in embryonic stem cells but to have no effect on the pathway in neuroprogenitor cells (57). Finally, it should be noted that other factors including FoxO1 (58) and NMP4-CIZ (12) have also been shown to modulate ␤-catenin activity in osteoblasts, with the actions of the latter being responsive to experimental loading.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-inducible Factor-1α Protein Negatively Regulates Load-induced Bone Formation

Riddle

Leslie

Gross

et al. 2011

Journal of Biological Chemistry

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Background:The mechanisms by which bone responds to changes in its loading environment are poorly understood. Results: Mechanical signals induce Hif-1␣ expression, and mice lacking Hif-1␣ in bone are more responsive to loading. Conclusion: Hif-1␣ is a novel regulator of skeletal mechanotransduction that impinges on Wnt signaling. Significance: Understanding skeletal mechanotransduction may lead to the development of therapies designed to enhance bone formation.

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Section: Discussionmentioning

confidence: 99%

Hypoxia-inducible Factor-1α Protein Negatively Regulates Load-induced Bone Formation

Riddle

Leslie

Gross

et al. 2011

Journal of Biological Chemistry

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“…Certain studies have suggested that HIF-1α activation regulates the Wnt/β-catenin signaling pathway, which activates the expression of target genes and contributes to the enhanced invasion of hypoxic gastric cancer cells (35)(36)(37). CD44 is a target gene of the Wnt/β-catenin signaling pathway (38); therefore, the mechanism by which HIF-1α regulates CD44 may be associated with the Wnt/β-catenin signaling pathway in gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia regulates CD44 expression via hypoxia-inducible factor-1α in human gastric cancer cells

Liang

et al. 2016

Oncology Letters

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Abstract. Hypoxia induces proliferation and invasion in cancer cells via hypoxia-inducible factor (HIF)-1α. The cell adhesion molecule cluster of differentiation (CD) 44 has been associated with increased cell invasion and metastasis. Whether hypoxia regulates the expression of CD44 in gastric cancer cells remains to be established. In the current study, the effects of hypoxia on HIF-1α and CD44 expression levels in human gastric cell lines SGC-7901 and BGC-823 were evaluated. The cells were cultured in 1% O 2 for 1 week and then treated with 20 nM rapamycin for 72 h. Cell viability was evaluated using the Cell Counting kit-8 assay, and cell invasion was detected by the Transwell invasion assay. The protein and messenger (m) RNA expression levels of HIF-1α and CD44 were detected using western blotting and reverse transcription-quantitative polymerase chain reaction, respectively. The results revealed that cell viability and invasion increased under hypoxic conditions, but decreased following rapamycin treatment in SGC-7901 and BGC-823 cells. Hypoxia also increased the protein and mRNA expression levels of HIF-1α and CD44 in these two cell lines. However, this hypoxia-induced increase in HIF-1α and CD44 protein and mRNA expression levels was inhibited by rapamycin. These findings suggest that hypoxia induced the proliferation and invasion of SGC-7901 and BGC-823 cells. Furthermore, CD44 expression levels were potentially associated with HIF-1α expression levels. Therefore, in gastric cancer cells, hypoxia may regulate CD44 expression via HIF-1α in order to promote cell proliferation and invasion.

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“…promoters that enhance tumor survival [446]. Strikingly, the promoters of genes of Tcf-1 and Lef-1contain hypoxia response elements (HREs) [451] and Hif-1 is directly involved in regulating Tcf/Lef protein abundance [451]. Hif-1 also is involved in regulating the transcription of proteins implied the destruction complex, and has been shown to negatively regulate the transcription of APC via hypoxia-responsive elements, which could lead to increased cellular -catenin levels.…”

Section: The -Catenin Tcf/lef Transcription Complexmentioning

confidence: 99%

Wnt/beta-Catenin Signaling and Small Molecule Inhibitors

Voronkov¹,

Krauß²

2012

CPD

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Wnt/ -catenin signaling is a branch of a functional network that dates back to the first metazoans and it is involved in a broad range of biological systems including stem cells, embryonic development and adult organs. Deregulation of components involved in Wnt/ -catenin signaling has been implicated in a wide spectrum of diseases including a number of cancers and degenerative diseases. The key mediator of Wnt signaling, -catenin, serves several cellular functions. It functions in a dynamic mode at multiple cellular locations, including the plasma membrane, where -catenin contributes to the stabilization of intercellular adhesive complexes, the cytoplasm where -catenin levels are regulated and the nucleus where -catenin is involved in transcriptional regulation and chromatin interactions. Central effectors of -catenin levels are a family of cysteine-rich secreted glycoproteins, known as Wnt morphogens. Through the LRP5/6-Frizzled receptor complex, Wnts regulate the location and activity of the destruction complex and consequently intracellularcatenin levels. However, -catenin levels and their effects on transcriptional programs are also influenced by multiple other factors including hypoxia, inflammation, hepatocyte growth factor-mediated signaling, and the cell adhesion molecule E-cadherin. The broad implications of Wnt/ -catenin signaling in development, in the adult body and in disease render the pathway a prime target for pharmacological research and development. The intricate regulation of -catenin at its various locations provides alternative points for therapeutic interventions.

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O2 regulates stem cells through Wnt/β-catenin signalling

Cited by 412 publications

References 33 publications

Hypoxia-inducible Factor-1α Protein Negatively Regulates Load-induced Bone Formation

Hypoxia-inducible Factor-1α Protein Negatively Regulates Load-induced Bone Formation

Hypoxia regulates CD44 expression via hypoxia-inducible factor-1α in human gastric cancer cells

Wnt/beta-Catenin Signaling and Small Molecule Inhibitors

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