A Wnt signaling pathway controls hox gene expression and neuroblast migration in C. elegans

Development ◽  
1999 ◽  
Vol 126 (1) ◽  
pp. 37-49 ◽  
Author(s):  
J.N. Maloof ◽  
J. Whangbo ◽  
J.M. Harris ◽  
G.D. Jongeward ◽  
C. Kenyon
Keyword(s):  
Gene Expression ◽  
Wnt Signaling ◽  
Wnt Pathway ◽  
Hox Genes ◽  
Wnt Signaling Pathway ◽  
Beta Catenin ◽  
Hox Gene ◽  
C Elegans ◽  
Neuroblast Migration ◽  
Pathway Gene

The specification of body pattern along the anteroposterior (A/P) body axis is achieved largely by the actions of conserved clusters of Hox genes. Limiting expression of these genes to localized regional domains and controlling the precise patterns of expression within those domains is critically important for normal patterning. Here we report that egl-20, a C. elegans gene required to activate expression of the Hox gene mab-5 in the migratory neuroblast QL, encodes a member of the Wnt family of secreted glycoproteins. We have found that a second Wnt pathway gene, bar-1, which encodes a beta-catenin/Armadillo-like protein, is also required for activation of mab-5 expression in QL. In addition, we describe the gene pry-1, which is required to limit expression of the Hox genes lin-39, mab-5 and egl-5 to their correct local domains. We find that egl-20, pry-1 and bar-1 all function in a linear genetic pathway with conserved Wnt signaling components, suggesting that a conserved Wnt pathway activates expression of mab-5 in the migratory neuroblast QL. Moreover, we find that members of this Wnt signaling system play a major role in both the general and fine-scale control of Hox gene expression in other cell types along the A/P axis.

scholarly journals Wnt Pathway Gene Expression Is Associated With Arterial Stiffness

2020 ◽  
Vol 9 (3) ◽  
Author(s):  
Allison L. Kuipers ◽  
Iva Miljkovic ◽  
Emma Barinas‐Mitchell ◽  
Cara S. Nestlerode ◽  
Ryan K. Cvejkus ◽  
...  
Keyword(s):  
Gene Expression ◽  
Arterial Stiffness ◽  
Pulse Wave Velocity ◽  
Wave Velocity ◽  
Wnt Pathway ◽  
Pulse Wave ◽  
Glycogen Synthase ◽  
African Ancestry ◽  
Wnt Signaling Pathway ◽  
Pathway Gene

Background Animal and in vitro experiments implicate the Wnt pathway in cardiac development, fibrosis, vascular calcification, and atherosclerosis, but research in humans is lacking. We examined peripheral blood Wnt pathway gene expression and arterial stiffness in 369 healthy African ancestry men (mean age, 64 years). Methods and Results Gene expression was assessed using a custom Nanostring nC ounter gene expression panel (N=43 genes) and normalized to housekeeping genes and background signal. Arterial stiffness was assessed via brachial‐ankle pulse‐wave velocity. Fourteen Wnt genes showed detectable expression and were tested individually as predictors of pulse‐wave velocity using linear regression, adjusting for age, height, weight, blood pressure, medication use, resting heart rate, current smoking, alcohol intake, and sedentary lifestyle. Adenomatous polyposis coli regulator of Wnt signaling pathway ( APC ), glycogen synthase kinase 3β ( GSK 3B ), and transcription factor 4 ( TCF 4 ) were significantly associated with arterial stiffness ( P <0.05 for all). When entered into a single model, APC and TCF 4 expression remained independently associated with arterial stiffness ( P =0.04 and 0.003, respectively), and each explained ≈3% of the variance in pulse‐wave velocity. Conclusions The current study establishes a novel association between in vivo expression of the Wnt pathway genes, APC and TCF 4 , with arterial stiffness in African ancestry men, a population at high risk of hypertensive vascular disease.

egl-27 generates anteroposterior patterns of cell fusion in C. elegans by regulating Hox gene expression and Hox protein function

Development ◽  
1999 ◽  
Vol 126 (15) ◽  
pp. 3303-3312 ◽  
Author(s):  
Q. Ch'ng ◽  
C. Kenyon
Keyword(s):  
Gene Expression ◽  
Cell Fusion ◽  
Protein Function ◽  
Hox Genes ◽  
Positional Information ◽  
Cell Fates ◽  
Hox Proteins ◽  
Hox Gene ◽  
C Elegans ◽  
Hox Protein

Hox genes pattern the fates of the ventral ectodermal Pn.p cells that lie along the anteroposterior (A/P) body axis of C. elegans. In these cells, the Hox genes are expressed in sequential overlapping domains where they control the ability of each Pn.p cell to fuse with the surrounding syncytial epidermis. The activities of Hox proteins are sex-specific in this tissue, resulting in sex-specific patterns of cell fusion: in hermaphrodites, the mid-body cells remain unfused, whereas in males, alternating domains of syncytial and unfused cells develop. We have found that the gene egl-27, which encodes a C. elegans homologue of a chromatin regulatory factor, specifies these patterns by regulating both Hox gene expression and Hox protein function. In egl-27 mutants, the expression domains of Hox genes in these cells are shifted posteriorly, suggesting that egl-27 influences A/P positional information. In addition, egl-27 controls Hox protein function in the Pn.p cells in two ways: in hermaphrodites it inhibits MAB-5 activity, whereas in males it permits a combinatorial interaction between LIN-39 and MAB-5. Thus, by selectively modifying the activities of Hox proteins, egl-27 elaborates a simple Hox expression pattern into complex patterns of cell fates. Taken together, these results implicate egl-27 in the diversification of cell fates along the A/P axis and suggest that chromatin reorganization is necessary for controlling Hox gene expression and Hox protein function.

CDX2 regulates Human Leukemogenesis Via Modulation Of The Wnt-Signaling Pathway

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3746-3746
Author(s):  
Anna Paczulla ◽  
Martina Konantz ◽  
Sarah Grzywna ◽  
Lothar Kanz ◽  
Claudia Lengerke
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Hox Genes ◽  
Wnt Signaling Pathway ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Nsg Mice ◽  
Cdx2 Expression

Abstract Introduction The caudal-type homeobox (Cdx) gene family has been mainly studied during early development for its role in axial elongation and antero-posterior patterning. More recently, Cdx genes were shown to regulate embryonic hematopoiesis by interactions with the canonical Wnt pathway and Hox genes. The role of Cdx genes in adult hematopoiesis remains poorly understood. Adult hematopoietic stem and progenitor cells derived from healthy murine bone marrow (BM) express low levels of Cdx1 and Cdx4 but not Cdx2. However, the majority (>80%) of human acute myeloid (AML) and lymphoid leukemias (ALL) were shown to express the human homologue CDX2, and ectopic induction of Cdx2 expression was sufficient to robustly induce myeloid leukemia in murine bone marrow cells. On the molecular level, the leukemogenic activity of Cdx2 was associated with modulation of Hox and Klf4 gene expression (Faber et al, 2013). The current study further explores the role of CDX2 in leukemogenesis by analyzing the effects of CDX2 expression induction or repression on human healthy and malignant hematopoietic cells and its molecular effects on the Wnt signaling pathway known to regulate Cdx genes during embryonic development. Methods Human bone marrow or mobilized peripheral blood derived CD34+ cells as well as the human leukemic cell lines SKM-1, NOMO-1, EOL-1 and NALM16 were exposed to lentiviruses containing CDX2 overexpression, shRNAs against CDX2 or control constructs. Efficient modulation of CDX2 expression was verified on gene expression level by qRT-PCR and on protein level by immunoblot analysis. CDX2 modified and control cells were subjected to growth, colony forming (CFU), cell cycle, flow cytometry and qRT-PCR gene expression analysis assays and analyzed in vivo upon xenotransplantation in NOD/SCID/IL2Rγnull (NSG) mice. To explore the effect of Dickkopf-1 (DKK1), recombinant human DKK1 protein or carrier was supplemented to the methylcellulose in CFU assays. Results shRNA-mediated knockdown of CDX2 in leukemic cell lines lead to reduced growth (SKM-1, NALM16) and CFU formation (SKM-1 cells). Consistently, CDX2 knockdown SKM-1 cells showed lower ability to repopulate NSG mice and, upon subcutaneous injection in the flank, gave rise to much smaller tumors when compared to control cells, supporting the notion that CDX2 plays roles in human leukemogenesis. In contrast to the data published in mice, healthy human CD34+ cells transduced to overexpress CDX2 were unable to induce leukemia upon transplantation in NSG mice within an observation period of 5 months. On the molecular level, CDX2 modified cells showed differential expression of Klf4 and Hox but also Wnt pathway associated genes. Notably, robust induction of the canonical Wnt-inhibitory molecule DKK1 was observed in both healthy CD34+ stem/progenitor and leukemic cells upon CDX2 induction, while CDX2 suppression showed opposite effects. Analysis of the DKK1 promotor region revealed an interspecies conserved putative binding site for CDX2 as well as multiple HOX gene binding sites, suggesting that CDX2 can modulate DKK1 expression directly but also via its downstream HOX genes. Importantly, CFU assays performed on CDX2-knockdown cells showed a rescue of colony formation upon stimulation with DKK1 protein as compared to treatment with carrier only, demonstrating that the observed molecular interaction is functionally relevant in human leukemic cells. In contrast, control leukemic cells treated with DKK1 showed reduced CFU formation, indicating that CDX2 might act through DKK1 activation to fine-tune Wnt signal activation to the dosage that best promotes leukemogenesis and leukemic cell growth and survival. Conclusion Taken together, our data indicate that CDX2 employs DKK1 activation to modulate the Wnt signaling pathway and thereby growth, clonogenic capacity as well as in vivo tumorigenicity of human leukemia cells. In contrast to murine cells, CDX2 activation requires cooperative molecular events in order to induce leukemia in human healthy stem and progenitor cells. Disclosures: No relevant conflicts of interest to declare.

scholarly journals P085 Expression profiling of Wnt pathway genes in colon biopsies of patients with Ulcerative Colitis

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S186-S186
Author(s):  
C Lu ◽  
D Shah ◽  
A Wijnands ◽  
B Oldenburg ◽  
W C Yeh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cell ◽  
Wnt Signaling ◽  
Wnt Pathway ◽  
Target Genes ◽  
Expression Patterns ◽  
Critical Role ◽  
Epithelial Regeneration ◽  
Pathway Gene ◽  
Wnt Signal

Abstract Background There is an increasing demand of agents that can promote mucosal healing in Inflammatory Bowel Disease (IBD). Wnt/β-catenin signaling plays a critical role in epithelial regeneration and repair, and stimulating regeneration in the damaged epithelium by modulating Wnt signaling has been suggested as a potential treatment option for IBD. To guide development of Wnt modulating therapeutic molecules for IBD, an understanding of how Wnt signaling may be altered in IBD tissues is required. While earlier work showed altered Wnt pathway gene expression in UC tissues, these studies failed to consider disease conditions (moderate vs severe) and patient treatment history on expression of the Wnt family genes. These previous studies utilized RT-qPCR or microarray and did not reveal how Wnt pathway gene expression might be affected specifically in the epithelium and in the adjacent stromal stem cell niche. Here we report our work investigating expression patterns of Wnt pathway genes in UC biopsies from 12 patients with moderate and severe disease. Patients had either received no anti-TNF treatment or had gone through anti-TNF treatment and partially responded to the treatment. Methods Expression of a set of Wnt pathway genes was assessed in UC colon and rectum biopsies by RNAscope in situ hybridization and compared to expression patterns in normal control colon. The genes included the Wnt target genes AXIN2, LGR5 and RNF43, Wnt ligands and the FZD5 and LRP6 receptors enriched in the intestinal epithelium as well as key Wnt signal modulators RSPO1-4. Results Expression of Wnt target genes were mildly reduced in the UC colon epithelium, while their expression in some crypts appeared much lower. Overall expression levels of Wnt pathway genes did not differ between moderate and severe UC colon and Wnt target gene expression was more affected in the anti-TNF treated colons, which may reflect more refractory disease. Expression of FZD5, LRP6 and the key niche factor RSPO2, was reduced in the UC colon. RSPOs are normally expressed in the stromal cells next to the crypt bottom stem cell compartment but this expression pattern was disrupted in the UC colon as a result of immune cell infiltration. Although expression of Wnts was induced in the UC colon tissues, the location of expression was altered due to tissue damage, potentially making the Wnts less accessible to the intestinal stem cells. Conclusion Reduced expression of Wnt receptors, RSPOs and Wnt target genes indicate insufficient Wnt signal induction in the damaged colon epithelium of UC patients. This suggests that repair of the damaged epithelium by Wnt agonist treatment may constitute a new mechanism of action and benefit patients with UC.

scholarly journals Mir-186-5p Regulates WNT Signaling Pathway by Targeting TCF4 Transcription Factor

2018 ◽  
Vol 8 (1) ◽  
pp. 132
Author(s):  
Zahra Bayat ◽  
Bahram M. Soltani
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Wnt Signaling ◽  
Cell Line ◽  
Signaling Pathway ◽  
Wnt Pathway ◽  
Wnt Signaling Pathway ◽  
Sw480 Cell ◽  
Sw480 Cell Line ◽  
Sw480 Cells

The evolutionarily conserved Wnt signaling pathway plays essential roles during embryonic development, tissue homeostasis and differentiation. This pathway is deregulated in many cancers especially colorectal cancer. MiRNAs are a class of small noncoding RNAs that may play a major role in post transcriptional regulation of many genes and signaling pathway such as WNT signaling pathway. Here, we intended to investigate if miR-186-5p is capable of regulating WNT signaling pathway wia suppression TCF4 gene expression. miR-186-5p was bioinformatically predicted as a candidate regulator of TCF4 gene expression and then, in this experimental study, miR-186-5p was overexpressed in SW480 cell line and its increased expression was detected through quantitative reverse transcription polymerase chain reaction (RT-qPCR). The effect of miR-186-5p on WNT pathway was analysied with TOP/FOP flash assay in SW480 cell line. Finally, flow cytometery was used to inves tigate the effect of miR-186-5p overexpression on cell cycle progression in SW480 cell line. miR-186-5p was overexpressed in the SW480 cell line and its overexpression resulted in significant reduction of the TCF4 mRNA level. TOP/FOP flash assay, confirmed the negative effect of miR-186-5p on the Wnt pathway in SW480 cells. Finally, Overexpression of miR186-5p in SW480 cells resulted in cell cycle arrest in subG1 phase, detected by flow cytometry. Overall, accumulative results indi-cated that miR-186-5p by targeting TCF4 is potentially one of the regulators of the WNT signaling pathway.

Identification of Genes That Regulate a Left-Right Asymmetric Neuronal Migration inCaenorhabditis elegans

Genetics ◽  
2003 ◽  
Vol 164 (4) ◽  
pp. 1355-1367 ◽  
Author(s):  
QueeLim Ch’ng ◽  
Lisa Williams ◽  
Yung S Lie ◽  
Mary Sym ◽  
Jennifer Whangbo ◽  
...  
Keyword(s):  
Cell Migration ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Neuronal Migration ◽  
Wnt Signaling Pathway ◽  
Hox Gene ◽  
C Elegans ◽  
Asymmetric Response ◽  
Left Right Asymmetry ◽  
Wnt Signal

AbstractIn C. elegans, cells of the QL and QR neuroblast lineages migrate with left-right asymmetry; QL and its descendants migrate posteriorly whereas QR and its descendants migrate anteriorly. One key step in generating this asymmetry is the expression of the Hox gene mab-5 in the QL descendants but not in the QR descendants. This asymmetry appears to be coupled to the asymmetric polarizations and movements of QL and QR as they migrate and relies on an asymmetric response to an EGL-20/Wnt signal. To identify genes involved in these complex layers of regulation and to isolate targets of mab-5 that direct posterior migrations, we screened visually for mutants with cell migration defects in the QL and QR lineages. Here, we describe a set of new mutants (qid-5, qid-6, qid-7, and qid-8) that primarily disrupt the migrations of the QL descendants. Most of these mutants were defective in mab-5 expression in the QL lineage and might identify genes that interact directly or indirectly with the EGL-20/Wnt signaling pathway.

Effects of SM08502, a novel, oral small-molecule inhibitor of Wnt pathway signaling, on gene expression and antitumor activity in colorectal cancer (CRC) models.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15185-e15185 ◽  
Author(s):  
Carine Bossard ◽  
Kevin Chiu ◽  
Heekyung Chung ◽  
John Duc Nguyen ◽  
Emily Creger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Antitumor Activity ◽  
Wnt Signaling ◽  
Cell Lines ◽  
Wnt Pathway ◽  
Pathway Gene ◽  
Hct 116

e15185 Background: Aberrant activation of Wnt signaling contributing to tumorigenesis is most commonly associated with CRC (90% harbor Wnt pathway mutations). SM08502, a novel, oral Wnt signaling pathway inhibitor, was evaluated in preclinical CRC models. Methods: In vitro Wnt signaling: assessed using TOPflash β-catenin/TCF reporter assay in SW480 human CRC cells. In vitro Wnt pathway gene expression: measured by qRT-PCR in SW480 and Wnt3a-stimulated cells (HEK-293T, IEC-6), and with the Nanostring Wnt pathway array (180 genes) across a panel of 16 CRC cell lines. In vitro cell proliferation: 17 CRC cell lines were used to test cell viability following treatment. In vivo antitumor activity: Oral SM08502 was tested in CRC mouse xenografts (SW480, HCT 116) and a PDX model over 20-21 days (QD, QOD). 24-hr pharmacodynamic (PD) analysis of Wnt pathway gene expression was done in SW480 tumor explants from mice following one 25 mg/kg dose. Results: SM08502 inhibited Wnt pathway signaling (EC50 = 46 nM) in SW480 cells. Wnt pathway gene expression was inhibited by SM08502 (0.3-3 µM) in Wnt3a-stimulated cells ( AXIN2, LEF1) and SW480 ( AXIN2, CTNNB1, LEF1, MYC, TCF7, TCF7L2) at 24 hrs ( P < .05 vs. vehicle) . Corresponding effects on protein expression were confirmed for all genes except CTNNB1, suggesting SM08502 acted independently of β-catenin. Nanostring array screening identified inhibition of LRP5, DVL2, BTRC, and ERBB2 by SM08502. Cell proliferation was inhibited in all 17 lines (avg. EC50 = 177 nM). In vivo, SM08502 was well tolerated and induced dose-dependent antitumor effects in xenografts and PDX models. Tumor growth inhibition for 25 mg/kg QD (max dose) was 83%, 56%, and 70% in SW480, HCT 116, and PDX, respectively. PD analysis showed significant inhibition ( P< .05 vs. vehicle) of TCF7, MYC, LRP5, DVL2, and BTRC expression 8 hrs post treatment. Conclusions: In preclinical CRC models, SM08502 was a potent inhibitor of Wnt pathway signaling and gene expression. It showed strong antitumor activity in human tumor models with activating Wnt pathway mutations. The safety, tolerability, and PK of SM08502 are being evaluated in an ongoing phase 1 study (NCT03355066).

scholarly journals Mir-186-5p Regulates WNT Signaling Pathway by Targeting TCF4 Transcription Factor

2018 ◽  
Vol 8 (1) ◽  
pp. 130
Author(s):  
Zahra Bayat ◽  
Bahram M. Soltani
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Wnt Signaling ◽  
Cell Line ◽  
Signaling Pathway ◽  
Wnt Pathway ◽  
Wnt Signaling Pathway ◽  
Sw480 Cell ◽  
Sw480 Cell Line ◽  
Sw480 Cells

The evolutionarily conserved Wnt signaling pathway plays essential roles during embryonic development, tissue homeostasis and differentiation. This pathway is deregulated in many cancers especially colorectal cancer. MiRNAs are a class of small noncoding RNAs that may play a major role in post transcriptional regulation of many genes and signaling pathway such as WNT signaling pathway. Here, we intended to investigate if miR-186-5p is capable of regulating WNT signaling pathway wia suppression TCF4 gene expression. miR-186-5p was bioinformatically predicted as a candidate regulator of TCF4 gene expression and then, in this experimental study, miR-186-5p was overexpressed in SW480 cell line and its increased expression was detected through quantitative reverse transcription polymerase chain reaction (RT-qPCR). The effect of miR-186-5p on WNT pathway was analysied with TOP/FOP flash assay in SW480 cell line. Finally, flow cytometery was used to inves tigate the effect of miR-186-5p overexpression on cell cycle progression in SW480 cell line. miR-186-5p was overexpressed in the SW480 cell line and its overexpression resulted in significant reduction of the TCF4 mRNA level. TOP/FOP flash assay, confirmed the negative effect of miR-186-5p on the Wnt pathway in SW480 cells. Finally, Overexpression of miR186-5p in SW480 cells resulted in cell cycle arrest in subG1 phase, detected by flow cytometry. Overall, accumulative results indi-cated that miR-186-5p by targeting TCF4 is potentially one of the regulators of the WNT signaling pathway.

scholarly journals Equine Genital Squamous Cell Carcinoma Associated with EcPV2 Infection: RANKL Pathway Correlated to Inflammation and Wnt Signaling Activation

Biology ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 244
Author(s):  
Samanta Mecocci ◽  
Ilaria Porcellato ◽  
Federico Armando ◽  
Luca Mechelli ◽  
Chiara Brachelente ◽  
...  
Keyword(s):  
Gene Expression ◽  
Wnt Signaling ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Animal Health ◽  
Wnt Signaling Pathway ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
Signaling Activation ◽  
Expression Evaluation

Equine genital squamous cell carcinomas (egSCCs) are among the most common equine tumors after sarcoids, severely impairing animal health and welfare. Equus caballus papillomavirus type 2 (EcPV2) infection is often related to these tumors. The aim of this study was to clarify the molecular mechanisms behind egSCCs associated with EcPV2 infection, investigating receptor activator of nuclear factor-kappa B ligand (RANKL) signaling in NF-kB pathway, together with the Wnt and IL17 signaling pathways. We analyzed the innate immune response through gene expression evaluation of key cytokines and transcription factors. Moreover, Ki67 index was assessed with immunohistochemistry. EcPV2-E6 DNA was checked, and viral presence was confirmed in 21 positive out to 23 cases (91%). Oncogene expression was confirmed in 14 cases (60.8%) for E6 and in 8 (34.7%) for E2. RANKL, nuclear factor kappa-light-chain-enhancer of activated B cells (NFKB)-p50, NFKBp65, interleukin (IL)-6, IL17, IL23p19, IL8, IL12p35, IL12p40, β-catenin (BCATN1), FOS like 1 (FOSL1), and lymphoid enhancer binding factor 1 (LEF1) showed a significant upregulation in tumor samples compared to healthy tissues. Our results describe an inflammatory environment characterized by the activation of RANKL/RANK and IL17 with the relative downstream pathways, and a positive modulation of inflammatory cytokines genes such as IL6 and IL8. Moreover, the increase of BCATN1, FOSL1, and LEF1 gene expression suggests an activation of both canonical and non-canonical Wnt signaling pathway that could be critical for carcinogenesis and tumor progression.

scholarly journals Regulation of Wnt Signaling by FOX Transcription Factors in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3446
Author(s):  
Stefan Koch
Keyword(s):  
Transcription Factors ◽  
Wnt Signaling ◽  
Wnt Pathway ◽  
Treatment Options ◽  
Wnt Signaling Pathway ◽  
Tissue Homeostasis ◽  
Fine Tuning ◽  
Dependent Manner ◽  
Forkhead Box ◽  
Signaling Activity

Aberrant activation of the oncogenic Wnt signaling pathway is a hallmark of numerous types of cancer. However, in many cases, it is unclear how a chronically high Wnt signaling tone is maintained in the absence of activating pathway mutations. Forkhead box (FOX) family transcription factors are key regulators of embryonic development and tissue homeostasis, and there is mounting evidence that they act in part by fine-tuning the Wnt signaling output in a tissue-specific and context-dependent manner. Here, I review the diverse ways in which FOX transcription factors interact with the Wnt pathway, and how the ectopic reactivation of FOX proteins may affect Wnt signaling activity in various types of cancer. Many FOX transcription factors are partially functionally redundant and exhibit a highly restricted expression pattern, especially in adults. Thus, precision targeting of individual FOX proteins may lead to safe treatment options for Wnt-dependent cancers.

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