Targeting the canonical Wnt/β‐catenin pathway in hematological malignancies

Ashihara, Eishi; Takada, Tetsuya; Maekawa, Taira

doi:10.1111/cas.12655

Cited by 102 publications

(73 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, APC (which promotes the degradation of β-catenin) was also downregulated by the shRNAs, but just missed the threshold of inclusion. Conversely, we noted upregulation of genes including CCND1 (cyclin D1) and SNAI2 (SLUG), both Wnt signaling target genes (39, 40) and WNT6 , which is known to inhibit myoblast proliferation but induce myoblast elongation (41). Taken together, these results suggest that suppression of SFRP3 in part activates β-catenin/Wnt signaling pathway as we had seen in the tumor xenografts.…”

Section: Resultsmentioning

confidence: 86%

Secreted Frizzled-Related Protein 3 (SFRP3) Is Required for Tumorigenesis of PAX3–FOXO1-Positive Alveolar Rhabdomyosarcoma

Kephart

Tiller

Crose

et al. 2015

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose Rhabdomyosarcoma is a soft tissue sarcoma associated with the skeletal muscle lineage. Of the two predominant subtypes, known as embryonal (eRMS) and alveolar (aRMS), aRMS has the poorer prognosis, with a 5-year survival rate of <50%. The majority of aRMS tumors express the fusion protein PAX3-FOXO1. As PAX3-FOXO1 has proven chemically intractable, the current study aims to identify targetable proteins that are downstream from or cooperate with PAX3-FOXO1 to support tumorigenesis. Experimental Design Microarray analysis of the transcriptomes of human skeletal muscle myoblasts expressing PAX3-FOXO1 revealed alteration of several Wnt pathway gene members, including secreted frizzled related protein 3 (SFRP3), a secreted Wnt pathway inhibitor. Loss-of-function using shRNAs against SFRP3 were used to interrogate the role of SFRP3 in human aRMS cell lines in vitro and conditional murine xenograft systems in vivo. The combination of SFRP3 genetic suppression and the chemotherapeutic agent vincristine was also examined. Results In vitro, suppression of SFRP3 inhibited aRMS cell growth, reduced proliferation accompanied by a G1 arrest and induction of p21, and induced apoptosis. In vivo, doxycycline-inducible suppression of SFRP3 reduced aRMS tumor growth and weight by more than three-fold, in addition to increasing myogenic differentiation and β-catenin signaling. The combination of SFRP3 suppression and vincristine was more effective at reducing aRMS cell growth in vitro than either treatment alone, and ablated tumorigenesis in vivo. Conclusions SFRP3 is necessary for the growth of human aRMS cells both in vitro and in vivo and is a promising new target for investigation in aRMS.

show abstract

Section: Resultsmentioning

confidence: 86%

Secreted Frizzled-Related Protein 3 (SFRP3) Is Required for Tumorigenesis of PAX3–FOXO1-Positive Alveolar Rhabdomyosarcoma

Kephart

Tiller

Crose

et al. 2015

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…In Wnt signal-on state, β-catenin translocates to the nucleus and facilitates cyclin D1 and MMP7 expressions by forming a complex with other transcriptional activators [29–31]. SND1 as a transcriptional coactivator stimulates the expressions of Smad2 and Smad4 in TGFβ1 pathway [28].…”

Section: Discussionmentioning

confidence: 99%

miR-320a functions as a suppressor for gliomas by targeting SND1 and β-catenin, and predicts the prognosis of patients

Liu

et al. 2017

Oncotarget

View full text Add to dashboard Cite

miR-320a downexpression contributes to tumorigenesis in several human cancers. However, the relevance of miR-320a to prognosis, proliferation and invasion in gliomas remains unclear. In this study, we demonstrated that miR-320a expression was decreased in human glioma tissues and cell lines. Moreover, miR-320a expression was inversely correlated with glioma grades and Ki-67 index, but positively correlated with patients’ survival. Contrarily, SND1 and β-catenin expressions were positively correlated with glioma grades and Ki-67 index, but inversely correlated with miR-320a expression and patients’ survival. Furthermore, two subgroups with distinct prognoses in our glioma patients of different grade, IDH status, age and KPS were identified according to expression of miR-320a, SND1 or β-catenin. Cox regression showed that miR-320a and SND1 were independent predictors and β-catenin was an auxiliary predictor for patients’ survival. miR-320a overexpression suppressed the G1/S phase transition, proliferation, migration and invasion of glioblastoma cells. Mechanistically, we validated SND1 and β-catenin as direct targets of miR-320a, and found that miR-320a overexpression increased SND1-inhibited tumor suppressor p21WAF1 and decreased Smad2, Smad4, MMP2, MMP7 and cyclinD1, the pivotal downstream effectors of SND1 or β-catenin. Our findings demonstrate the potential values of miR-320a, SND1 and β-catenin as prognostic biomarkers and therapeutic candidates for malignant gliomas.

show abstract

“…Consistently in many tissue types, dysregulation of Wnt pathway has been strongly associated with expansion of stem and/progenitor cell lineages, as well as carcinogenesis [138]. Hence, therapies targeting Wnt pathway may lead to treatment options in hematological malignancies [139], liver cancer [140], and other type of tumors [141]. …”

Section: Introductionmentioning

confidence: 99%

Stemness-related markers in cancer

2017

View full text Add to dashboard Cite

Cancer stem cells (CSCs), with their self-renewal ability and multilineage differentiation potential, are a critical subpopulation of tumor cells that can drive tumor initiation, growth, and resistance to therapy. Like embryonic and adult stem cells, CSCs express markers that are not expressed in normal somatic cells and are thus thought to contribute towards a ‘stemness’ phenotype. This review summarizes the current knowledge of stemness-related markers in human cancers, with a particular focus on important transcription factors, protein surface markers and signaling pathways.

show abstract

Targeting the canonical Wnt/β‐catenin pathway in hematological malignancies

Cited by 102 publications

References 75 publications

Secreted Frizzled-Related Protein 3 (SFRP3) Is Required for Tumorigenesis of PAX3–FOXO1-Positive Alveolar Rhabdomyosarcoma

Secreted Frizzled-Related Protein 3 (SFRP3) Is Required for Tumorigenesis of PAX3–FOXO1-Positive Alveolar Rhabdomyosarcoma

miR-320a functions as a suppressor for gliomas by targeting SND1 and β-catenin, and predicts the prognosis of patients

Stemness-related markers in cancer

Contact Info

Product

Resources

About