Wnt target genes and where to find them

Ramakrishnan, Aravinda-Bharathi; Cadigan, Ken M.

doi:10.12688/f1000research.11034.1

Cited by 83 publications

(69 citation statements)

References 110 publications

(142 reference statements)

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“…While invertebrates contain one TCF, which participates in both sides of the transcriptional switch (Figure B), the presence of multiple TCFs in vertebrates has long raised the question of whether they have specialized transcriptional functions. Many genetic studies support the view that TCF3 (also known as TCF7L1) is a dedicated repressor and LEF1 a dedicated activator of Wnt targets, while TCF1 and TCF4 (also termed TCF7 and TCF7L2, respectively) display either activity depending on the context . Partially supporting this, TCF3 and TCF4 bind to TLEs with higher affinity than LEF1 or TCF1 .…”

Section: Is Tcf3 a Dedicated Repressor In The Transcriptional Switch?mentioning

confidence: 95%

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The Wnt Transcriptional Switch: TLE Removal or Inactivation?

et al. 2017

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Many targets of the Wnt/β-catenin signaling pathway are regulated by TCF transcription factors, which play important roles in animal development, stem cell biology, and oncogenesis. TCFs can regulate Wnt targets through a "transcriptional switch," repressing gene expression in unstimulated cells and promoting transcription upon Wnt signaling. However, it is not clear whether this switch mechanism is a general feature of Wnt gene regulation or limited to a subset of Wnt targets. Co-repressors of the TLE family are known to contribute to the repression of Wnt targets in the absence of signaling, but how they are inactivated or displaced by Wnt signaling is poorly understood. In this mini-review, we discuss several recent reports that address the prevalence and molecular mechanisms of the Wnt transcription switch, including the finding of Wnt-dependent ubiquitination/inactivation of TLEs. Together, these findings highlight the growing complexity of the regulation of gene expression by the Wnt pathway.

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Section: Is Tcf3 a Dedicated Repressor In The Transcriptional Switch?mentioning

confidence: 95%

“…The Wnt pathway facilitates short‐range signaling during development and in adult tissues. It has important roles in stem cell homeostasis and in the etiology of several cancers and human diseases . Transcriptional regulation by the Wnt pathway begins with the stabilization and nuclear accumulation of β‐catenin .…”

Section: Introductionmentioning

confidence: 99%

The Wnt Transcriptional Switch: TLE Removal or Inactivation?

et al. 2017

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“…This signaling pathway is conserved throughout metazoans and is essential for cell proliferation, differentiation, development, self-renewal, and cell fate determination [29, 30]. Much evidence has suggested that the Wnt/β-catenin signaling pathway acts as a key regulator in PEMF-induced osteogenic differentiation of mesenchymal progenitor cells, bone formation and repair.…”

Section: Underlying Signaling Pathwaysmentioning

confidence: 99%

Underlying Signaling Pathways and Therapeutic Applications of Pulsed Electromagnetic Fields in Bone Repair

Yuan

Xin

Jiang

2018

Cell Physiol Biochem

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Pulsed electromagnetic field (PEMF) stimulation, as a prospective, noninvasive, and safe physical therapy strategy to accelerate bone repair has received tremendous attention in recent decades. Physical PEMF stimulation initiates the signaling cascades, which effectively promote osteogenesis and angiogenesis in an orchestrated spatiotemporal manner and ultimately enhance the self-repair capability of bone tissues. Considerable research progresses have been made in exploring the underlying cellular and subcellular mechanisms of PEMF promotion effect in bone repair. Moreover, the promotion effect has shown strikingly positive benefits in the treatment of various skeletal diseases. However, many preclinical and clinical efficacy evaluation studies are still needed to make PEMFs more effective and extensive in clinical application. In this review, we briefly introduce the basic knowledge of PEMFs on bone repair, systematically elaborate several key signaling pathways involved in PEMFs-induced bone repair, and then discuss the therapeutic applications of PEMFs alone or in combination with other available therapies in bone repair, and evaluate the treatment effect by analyzing and summarizing recent literature.

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“…In particular, developmental signaling pathways and abnormal reactivation of transcription factors in tumor cells are closely related to advanced and aggressive cancers [7, 8]. Limb-bud and heart (LBH) is an important transcription cofactor involved in embryonic development [9].…”

Section: Introductionmentioning

confidence: 99%

Limb-Bud and Heart Attenuates Growth and Invasion of Human Lung Adenocarcinoma Cells and Predicts Survival Outcome

Deng

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: The transcription cofactor limb-bud and heart (LBH) is involved in embryonic development. However, its role in human lung cancer, especially lung adenocarcinoma (LUAD), remains unclear. Methods: A public database and tissue microarray (TMA) were used to compare differences in LBH expression and its relationship with clinical characteristics. Tissue from an additional 70 LUAD patients with follow-up records was used to explore the correlation of LBH expression with prognosis. Cellular and molecular studies validated the role of LBH in LUAD growth and invasion. Results: LBH was significantly down-regulated in lung cancer tissue samples and was correlated with the prognosis and clinical characteristics of lung cancer patients based on a public database and TMA. Survival analysis revealed that LBH-negative expression was associated with poor overall survival of LUAD patients (P = 0.021). Cox regression analysis showed that LBH expression status was a favorable independent prognostic factor (hazard ratio = 0.120, 95% confidence interval = 0.016–0.894, P = 0.039). LBH knockdown accelerated LUAD cell proliferation, migration, and invasion. Furthermore, bioinformatics analysis indicated that LBH was significantly related to the cell adhesion pathway. Western blot analysis confirmed that LBH could regulate the expression of integrin family members (integrin-α1, integrin-α2, integrin-α4, integrin-αv, and integrin-β4). Conclusion: Our data suggest that LBH plays an important role in lung cancer. Importantly, LBH is an independent prognostic factor in LUAD and can attenuate cell growth and invasion. LBH may be a potential prognostic biomarker in LUAD patients.

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Wnt target genes and where to find them

Cited by 83 publications

References 110 publications

The Wnt Transcriptional Switch: TLE Removal or Inactivation?

The Wnt Transcriptional Switch: TLE Removal or Inactivation?

Underlying Signaling Pathways and Therapeutic Applications of Pulsed Electromagnetic Fields in Bone Repair

Limb-Bud and Heart Attenuates Growth and Invasion of Human Lung Adenocarcinoma Cells and Predicts Survival Outcome

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