Regulation of Wnt Signaling by FOX Transcription Factors in Cancer

Koch, Stefan

doi:10.3390/cancers13143446

Cited by 23 publications

(17 citation statements)

References 147 publications

(201 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FOX proteins are transcription factors that regulate embryonic development and tissue homeostasis, and they are highly conserved across species. There are 44 FOX family members in humans, which are subclassified into 19 classes (A to S) based on sequence resemblance of the DNA-binding forkhead domain [ 42 ]. Functional studies of FOX have revealed that transcriptional activity differs markedly even when the domain sequences are similar.…”

Section: Downstream Wnt/β-catenin Master Genes Define the Hcc Dual Phenotypementioning

confidence: 99%

“…Evidence suggests that this close association between FOX transcription factors and the Wnt pathway contributes to cancer initiation and progression. The FOX family includes both activators and inhibitors of the Wnt pathway [ 42 ]. The Wnt pathway activators FOXM1 and FOXG1 have been reported to be expressed in HCC.…”

Section: Downstream Wnt/β-catenin Master Genes Define the Hcc Dual Phenotypementioning

confidence: 99%

See 1 more Smart Citation

Clinical Significance of the Duality of Wnt/β-Catenin Signaling in Human Hepatocellular Carcinoma

Aoki

Nishida

Kudo

2022

Cancers

View full text Add to dashboard Cite

Combination therapy with immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor inhibitors has been approved as a first-line treatment for unresectable hepatocellular carcinoma (HCC), indicating a critical role of ICIs in the treatment of HCC. However, 20% of patients do not respond effectively to ICIs; mutations in the activation of the Wnt/β-catenin pathway are known to contribute to primary resistance to ICIs. From this point of view, non-invasive detection of Wnt/β-catenin activation should be informative for the management of advanced HCC. Wnt/β-catenin mutations in HCC have a dual aspect, which results in two distinct tumor phenotypes. HCC with minimal vascular invasion, metastasis, and good prognosis is named the “Jekyll phenotype”, while the poorly differentiated HCC subset with frequent vascular invasion and metastasis, cancer stem cell features, and high serum Alpha fetoprotein levels, is named the “Hyde phenotype”. To differentiate these two HCC phenotypes, a combination of the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging and fluoro-2-deoxy-D-glucose-PET/CT may be useful. The former is applicable for the detection of the Jekyll phenotype, as nodules present higher enhancement on the hepatobiliary phase, while the latter is likely to be informative for the detection of the Hyde phenotype by showing an increased glucose uptake.

show abstract

Section: Downstream Wnt/β-catenin Master Genes Define the Hcc Dual Phenotypementioning

confidence: 99%

Section: Downstream Wnt/β-catenin Master Genes Define the Hcc Dual Phenotypementioning

confidence: 99%

Clinical Significance of the Duality of Wnt/β-Catenin Signaling in Human Hepatocellular Carcinoma

Aoki

Nishida

Kudo

2022

Cancers

View full text Add to dashboard Cite

show abstract

“…We also investigated the underlying molecular mechanism of FOXS1 in EMT. Current literature suggests that Wnt/β-catenin pathway is essential for EMT of gastrointestinal cancer [10,11] and half of all mammalian FOX transcription factors have been assigned a role in the Wnt pathway [16], primarily in cancer cells. Given these considerations, we analyzed Wnt/β-catenin signaling pathway-related proteins in LoVo and SW620 cells 48 h after transfection with or without siRNA by Western blotting.…”

Section: Foxs1 Is a Regulator Of The Wnt/β-catenin Pathwaymentioning

confidence: 99%

Forkhead Box S1 mediates epithelial-mesenchymal transition through the Wnt/β-catenin signaling pathway to regulate colorectal cancer progression

et al. 2022

View full text Add to dashboard Cite

Background Recent studies have shown that the fox family plays a vital role in tumorigenesis and progression. Forkhead Box S1 (FOXS1), as a newly identified subfamily of the FOX family, is overexpressed in certain types of malignant tumors and closely associated with patient's prognosis. However, the role and mechanism of the FOXS1 in colorectal cancer (CRC) remain unclear. Method FOXS1 level in CRC tissues and cell lines was analyzed by western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry (IHC) was used to detect the relationship between FOXS1 expression and clinicopathological features in 136 patients in our unit. The expression of FOXS1 was knocked down in CRC cells using small interfering RNA (siRNA) technology. Cell proliferation was assessed by CCK8 assay, colony formation, and 5-Ethynyl-20-deoxyuridine (EdU) incorporation assay. Flow cytometry detected apoptosis and wound healing, and Transwell assays determined cell migration and invasion. Western blotting was used to detect the levels of proteins associated with the Wnt/β-catenin signaling pathway. Then, we used short hairpin RNA (shRNA) to knock down FOXS1 to see the effect of FOXS1 on the proliferation, migration, invasion, and metastasis of CRC cells in vivo. Finally, we investigated the impact of Wnt activator LiCl on the proliferation, migration, invasion, and metastasis of CRC cells after FOXS1 knockdown. Result Compared to those in normal groups, FOXS1 overexpressed in CRC tissues and CRC cells (P < 0.05). Upregulation of FOXS1 association with poor prognosis of CRC patients. si-FOXS1 induced apoptosis and inhibited proliferation, migration, invasion, the epithelial-mesenchymal transition (EMT), and the Wnt/β-catenin signaling pathway in vitro; sh-FOXS1 inhibited the volume and weight of subcutaneous xenografts and the number of lung metastases in vivo. LiCl, an activator of Wnt signaling, partially reversed the effect of FOXS1 overexpression on CRC cells. Conclusion FOXS1 could function as an oncogene and promote CRC cell proliferation, migration, invasion and metastasis through the Wnt/βcatenin signaling pathway, FOXS1 may be a potential target for CRC treatment.

show abstract

“…The transcription factor forkhead box (FOX) is a family with a highly conserved winged-helix DNA-binding domain ( 1 , 2 ). FOX family members are involved in cell growth, differentiation, aging and carcinogenesis, and various regulatory and functional activities ( 3 , 4 ). From FOXA to FOXR, there are 17 gene subfamilies of FOX and more than 14 have been identified in humans ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

FOXC2 as a prognostic marker and a potential molecular target in patients with human solid tumors

Zhang

He²,

Tu³

et al. 2022

Front. Surg.

View full text Add to dashboard Cite

BackgroundForkhead Box Protein C2 (FOXC2) belongs to the Forkhead/Wing-helix family. The regulatory role of this transcription factor in physiological function and carcinogenic activity has been proven in subsequent investigations. However, there is still scarcity of evidence on the relationship between FOXC2 expression and prognosis in human solid tumors. We conducted this meta-analysis to evaluate the role of FOXC2 as a prognosis factor and a possible target marker in human solid tumors.MethodsPubMed, Web of Science, Embase, and the Cochrane library database were all searched methodically. Eligible publications on FOXC2 in human solid tumors were gathered and reviewed. The effect sizes were calculated using pooled hazard ratios (HRs) or odds ratios (ORs) with the corresponding 95% confidence interval (CI). Statistical analysis was conducted with Stata SE12.0.ResultsThis meta-analysis comprised 3,267 patients from 20 studies covering a variety of solid tumors. Increased FOXC2 expression was related to shorter overall survival (OS) (HR = 2.05, 95% CI: 1.73–2.42). High expression of FOXC2 is associated with lymph node metastases (OR = 3.33, 95% CI: 2.65–4.19), TNM stage (OR = 3.09, 95% CI: 2.00–4.78), and age (OR = 1.26, 95% CI: 1.06–1.50), according to the pooled ORs. However, no significant association was observed between the high expression of FOXC2 and sex, tumor size or tumor differentiation.ConclusionIncreased expression of FOXC2 is associated with unfavored OS, lymph node metastases, TNM stage, and age. FOXC2 is a promising prognostic marker and a novel target marker in human solid tumors.

show abstract

Regulation of Wnt Signaling by FOX Transcription Factors in Cancer

Cited by 23 publications

References 147 publications

Clinical Significance of the Duality of Wnt/β-Catenin Signaling in Human Hepatocellular Carcinoma

Clinical Significance of the Duality of Wnt/β-Catenin Signaling in Human Hepatocellular Carcinoma

Forkhead Box S1 mediates epithelial-mesenchymal transition through the Wnt/β-catenin signaling pathway to regulate colorectal cancer progression

FOXC2 as a prognostic marker and a potential molecular target in patients with human solid tumors

Contact Info

Product

Resources

About