Targeting Wnt signaling in colorectal cancer. A Review in the Theme: Cell Signaling: Proteins, Pathways and Mechanisms

Novellasdemunt, Laura; Antas, Pedro; Li, Vivian

doi:10.1152/ajpcell.00117.2015

Cited by 295 publications

(248 citation statements)

References 125 publications

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“…Importantly, unlike in carcinomas where activation of the Wnt/β-catenin pathway is associated with increased tumorigenesis and decreased patient survival (Kahn, 2014; Novellasdemunt et al, 2015), in melanomas the role of β-catenin is controversial (Kuphal and Bosserhoff, 2011; Webster et al, 2015). The majority of studies have reported that nuclear β–catenin levels decrease in metastatic melanoma specimen and cell lines (Bachmann et al, 2005; Kuphal and Bosserhoff, 2011).…”

Section: Discussionmentioning

confidence: 99%

Melanoma Suppressor Functions of the Carcinoma Oncogene FOXQ1

et al. 2017

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SUMMARY Opposite lineage-specific regulation of tumor progression by the same transcription factor is an understudied phenomenon. Here, we report that levels of a carcinoma oncogenic transcription factor FOXQ1 are decreased during melanoma progression. Moreover, in melanoma cells, FOXQ1 suppresses the same processes it activates in carcinoma cells: epithelial-to-mesenchymal transition, invasion, and metastasis. We identify that lineage-specific tumor suppressor or oncogenic functions of FOXQ1 in large part depend on its ability to repress or activate expression of the same gene (N-cadherin, (CDH2)) in melanoma or carcinoma cells, respectively. Mechanistically, we demonstrate that FOXQ1 interacts with nuclear β-catenin and TLE proteins, and that repression of CDH2 by FOXQ1 occurs in the presence of TLE and absence of nuclear β-catenin, levels of which are lower in human melanomas than carcinomas. Accordingly, FOXQ1-dependent phenotypes can be manipulated by altering nuclear β-catenin or TLE proteins levels. Our data identify a novel melanoma suppressor and establish a unique mechanism underlying inverse lineage-specific transcriptional regulation of transformed phenotypes.

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Section: Discussionmentioning

confidence: 99%

Melanoma Suppressor Functions of the Carcinoma Oncogene FOXQ1

et al. 2017

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“…Wnt signaling acts to maintain mammalian ISCs, regulate progenitor proliferation, and control differentiation of ISCs into secretory cells [49]. Furthermore, mutations in the tumor suppressor Adenomatous polyposis coli (Apc), a negative regulator of the Wnt signaling pathway, results in adenomas, which when combined with other mutations will progress to colon carcinoma [49]. In 2008 Lin and colleagues presented evidence that the wg ligand was expressed in visceral circular muscle, which is located directly underneath the ISCs [50].…”

Section: Feedback Regulation Of Intestinal Cell Proliferationmentioning

confidence: 99%

Maintenance of the adult Drosophila intestine: all roads lead to homeostasis

Guo

Lucchetta

Rafel

et al. 2016

Current Opinion in Genetics & Development

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Maintenance of tissue homeostasis is critical in tissues with high turnover such as the intestinal epithelium. The intestinal epithelium is under constant cellular assault due to its digestive functions and its function as a barrier to chemical and bacterial insults. The resulting high rate of cellular turnover necessitates highly controlled mechanisms of regeneration to maintain the integrity of the tissue over the lifetime of the organism. Transient increase in stem cell proliferation is a commonly used and elaborate mechanism to ensure fast and efficient repair of the gut. However, tissue repair is not limited to regulating ISC proliferation, as emerging evidence demonstrates that the Drosophila intestine uses multiple strategies to ensure proper tissue homeostasis that may also extend to other tissues.

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“…A growing body of research links this pathway with cancer cells expressing a CRC stem cell phenotype. The stem cell phenotype is associated with tumor chemoresistance through the upregulation of transporters involved in drug efflux [38]. …”

Section: Novel Therapeutic Optionsmentioning

confidence: 99%

Promising New Agents for Colorectal Cancer

Das

Ciombor

Haraldsdóttir

et al. 2018

Curr. Treat. Options in Oncol.

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Choosing the optimal treatment approach for patients with metastatic colorectal cancer (mCRC) demands that oncologists assess both clinical and genomic variables and individualize care based upon the findings. Clinically, choices depend on assessing the side of the colon in which the primary tumor originates, the sites and burden of metastatic disease, the patient's performance status, and their individual comorbidities. Genomic assessment of the tumor to discern the mutational status of genes such as RAS/RAF, HER2, and TRK, as well as assessing whether tumors have defective mismatch repair (dMMR) or high microsatellite instability (MSI-H), all factor in to potential treatment options and can determine clinical trial eligibility. Metastasectomy may be an option for patients with a low burden of disease and accessible liver- or lung-limited metastases. In some unresectable cases, systemic therapy with a FOLFOX- or FOLFIRI-based regimen with or without a biologic agent can lead to sufficient disease reduction to make a patient eligible for resection of metastatic disease. Tumor sidedness and RAS mutational status guide which biologic we add to the initial chemotherapy backbone, with patients with left-sided, RAS wild-type (WT) tumors receiving anti-epidermal growth factor receptor (EGFR)-directed therapy and patients with right-sided tumors or those with RAS mutations receiving bevacizumab. In patients with tumors that manifest microsatellite instability or deficient mismatch repair, we typically administer checkpoint inhibitors such as pembrolizumab or nivolumab after progression on irinotecan- or oxaliplatin-based therapies. In patients with progressive disease, we routinely send tumor tissue for next generation sequencing (NGS) to assess for the presence of actionable genomic alterations such as HER2, BRAF, and TRK fusions and offer them the option of enrollment on clinical trials with agents targeting those or other identified alterations.

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Targeting Wnt signaling in colorectal cancer. A Review in the Theme: Cell Signaling: Proteins, Pathways and Mechanisms

Cited by 295 publications

References 125 publications

Melanoma Suppressor Functions of the Carcinoma Oncogene FOXQ1

Melanoma Suppressor Functions of the Carcinoma Oncogene FOXQ1

Maintenance of the adult Drosophila intestine: all roads lead to homeostasis

Promising New Agents for Colorectal Cancer

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