A Necessary Role for Cyclin D2 Induction During Colon Cancer Progression Mediated by L1.

The cell adhesion molecule L1CAM (L1), mainly known for its function in brain cells, is a Wnt/β-catenin signaling target gene in colorectal cancer (CRC) cells, where it promotes invasion and liver metastasis. We interrogated which genes are expressed at increased levels in human CRC tissue and induced in CRC cell lines overexpressing L1. We found increased cyclin D2 levels in CRC tissue and LS 174T and HCT 116 human CRC cells overexpressing L1.

An Increase in Mucin2 Expression Is Required for Colon Cancer Progression Mediated by L1.

An induction in the expression of the cell adhesion receptor L1, a Wnt target gene, is a characteristic feature of Wnt/β-catenin activation in colon cancer cells at later stages of the disease. We investigated the proteins secreted following L1 expression in colon cancer cells and identified Mucin2 among the most abundant secreted proteins. We found that suppressing Mucin2 expression in L1-expressing colon cancer cells inhibits cell proliferation, motility, tumorigenesis, and liver metastasis.

Downregulation of the Tumor Suppressor TFF1 Is Required during Induction of Colon Cancer Progression by L1.

The immunoglobulin family cell adhesion receptor L1 is induced in CRC cells at the invasive front of the tumor tissue, and confers enhanced proliferation, motility, tumorigenesis, and liver metastasis. To identify putative tumor suppressors whose expression is downregulated in L1-expressing CRC cells, we blocked the L1-ezrin-NF-κB signaling pathway and searched for genes induced under these conditions. We found that TFF1, a protein involved in protecting the mucus epithelial layer of the colon, is downregulated in L1-expressing cells and displays characteristics of a tumor suppressor.

A Necessary Role for Increased Biglycan Expression during L1-Mediated Colon Cancer Progression.

Aberrant activation of Wnt/β-catenin signaling and downstream β-catenin-TCF target genes is a hallmark of colorectal cancer (CRC) development. We identified the immunoglobulin-like cell adhesion receptor L1CAM (L1) as a target of β-catenin-TCF transactivation in CRC cells. Overexpression of L1 in CRC cells confers enhanced proliferation, motility, tumorigenesis, and liver metastasis, and L1 is exclusively localized at invasive areas of human CRC tissue.

The Collagen-Modifying Enzyme PLOD2 Is Induced and Required during L1-Mediated Colon Cancer Progression.

The overactivation of Wnt/β-catenin signaling is a hallmark of colorectal cancer (CRC) development. We identified the cell adhesion molecule L1CAM (L1) as a target of β-catenin-TCF transactivation in CRC cells. The overexpression of L1 in CRC cells confers enhanced proliferation, motility, tumorigenesis and liver metastasis, and L1 is exclusively localized in the invasive areas of human CRC tissue.

Wnt/β-Catenin Target Genes in Colon Cancer Metastasis: The Special Case of L1CAM.

Cell adhesion to neighboring cells is a fundamental biological process in multicellular organisms that is required for tissue morphogenesis. A tight coordination between cell-cell adhesion, signaling, and gene expression is a characteristic feature of normal tissues. Changes, and often disruption of this coordination, are common during invasive and metastatic cancer development.

Recent insights into the role of L1CAM in cancer initiation and progression.

First described as a neuronal cell adhesion molecule, L1CAM was later identified to be present at increased levels in primary tumors and metastases of various types of cancer. Here, we describe the multifaceted roles of L1CAM that are involved in diverse fundamental steps during tumor initiation and progression, as well as in chemoresistance. Recently, Ganesh et al reported that L1CAM identifies metastasis-initiating cells in colorectal carcinoma exhibiting stem-like cell features, increased tumorigenic potential and enhanced chemoresistance.

ISG15 induction is required during L1-mediated colon cancer progression and metastasis.

Hyperactivation of Wnt/β-catenin target gene expression is a hallmark of colorectal cancer (CRC) development. We identified L1-CAM (L1) and Nr-CAM, members of the immunoglobulin family of nerve cell adhesion receptors, as target genes of the Wnt/β-catenin pathway in CRC cells. L1 overexpression in CRC cells enhances their motile and tumorigenic capacity and promotes liver metastasis.

Increased expression of cathepsin D is required for L1-mediated colon cancer progression.

Hyperactivation of Wnt/β-catenin target genes is considered a key step in human colorectal cancer (CRC) development. We previously identified the immunoglobulin-like cell adhesion receptor L1 as a target gene of β-catenin/TCF transactivation that is localized at the invasive edge of CRC tissue. Using gene arrays, we discovered a number of downstream target genes and signaling pathways conferred by L1 overexpression during colon cancer progression.

Cell-cell adhesion: linking Wnt/β-catenin signaling with partial EMT and stemness traits in tumorigenesis.

Changes in cell adhesion and motility are considered key elements in determining the development of invasive and metastatic tumors. Co-opting the epithelial-to-mesenchymal transition (EMT) process, which is known to occur during embryonic development, and the associated changes in cell adhesion properties in cancer cells are considered major routes for tumor progression. More recent studies in tumor tissues and circulating tumor cell clusters suggest a stepwise EMT process rather than an "all-or-none" transition during tumor progression.

The intestinal stem cell regulating gene ASCL2 is required for L1-mediated colon cancer progression.

Aberrant Wnt/β-catenin signaling is a common event during human colorectal cancer (CRC) development. Previously, we characterized members of the L1 family of cell adhesion receptors as targets of β-catenin-LEF1/TCF transactivation that are expressed at the invasive CRC tissue edge. Overexpression of L1 in CRC cells confers enhanced motility, tumorigenesis and liver metastasis.

The Wnt Target Gene L1 in Colon Cancer Invasion and Metastasis.

The Wnt-β-catenin signaling pathway is highly conserved during evolution and determines normal tissue homeostasis. Hyperactivation of Wnt-β-catenin signaling is a characteristic feature of colorectal cancer (CRC) development. β-catenin is a major transducer of the Wnt signal from the cytoplasm into the nucleus where it acts as a co-transcriptional activator of β-catenin-TCF target genes.

Wnt signaling in cancer stem cells and colon cancer metastasis.

Overactivation of Wnt signaling is a hallmark of colorectal cancer (CRC). The Wnt pathway is a key regulator of both the early and the later, more invasive, stages of CRC development. In the normal intestine and colon, Wnt signaling controls the homeostasis of intestinal stem cells (ISCs) that fuel, via proliferation, upward movement of progeny cells from the crypt bottom toward the villus and differentiation into all cell types that constitute the intestine.

Clusterin, a gene enriched in intestinal stem cells, is required for L1-mediated colon cancer metastasis.

Hyperactive Wnt signaling is a common feature in human colorectal cancer (CRC) cells. A central question is the identification and role of Wnt/β-catenin target genes in CRC and their relationship to genes enriched in colonic stem cells, since Lgr5+ intestinal stem cells were suggested to be the cell of CRC origin. Previously, we identified the neural immunoglobulin-like adhesion receptor L1 as a Wnt/β-catenin target gene localized in cells at the invasive front of CRC tissue and showed that L1 expression in CRC cells confers enhanced motility and liver metastasis.

c-Kit is suppressed in human colon cancer tissue and contributes to L1-mediated metastasis.

The transmembrane neural cell adhesion receptor L1 is a Wnt/β-catenin target gene expressed in many tumor types. In human colorectal cancer, L1 localizes preferentially to the invasive front of tumors and when overexpressed in colorectal cancer cells, it facilitates their metastasis to the liver. In this study, we investigated genes that are regulated in human colorectal cancer and by the L1-NF-κB pathway that has been implicated in liver metastasis.

Coordinating changes in cell adhesion and phenotype during EMT-like processes in cancer.

Understanding the progression of a primary cancer to the metastatic stage has been the focus of extensive research for years. Commonly accepted concepts in this process (i.e.

L1-mediated colon cancer cell metastasis does not require changes in EMT and cancer stem cell markers.

Aberrant activation of Wnt/β-catenin signaling is common in most sporadic and inherited colorectal cancer (CRC) cells leading to elevated β-catenin/TCF transactivation. We previously identified the neural cell adhesion molecule L1 as a target gene of β-catenin/TCF in CRC cells. Forced expression of L1 confers increased cell motility, invasion, and tumorigenesis, and the induction of human CRC cell metastasis to the liver.

Nuclear factor-kappaB signaling and ezrin are essential for L1-mediated metastasis of colon cancer cells.

Hyperactivation of beta-catenin-T-cell-factor (TCF)-regulated gene transcription is a hallmark of colorectal cancer (CRC). The cell-neural adhesion molecule L1CAM (hereafter referred to as L1) is a target of beta-catenin-TCF, exclusively expressed at the CRC invasive front in humans. L1 overexpression in CRC cells increases cell growth and motility, and promotes liver metastasis.

The cell adhesion nectin-like molecules (Necl) 1 and 4 suppress the growth and tumorigenic ability of colon cancer cells.

A key step in human colon cancer development includes the hyperactivation of Wnt/beta-catenin signaling and the induction of beta-catenin-TCF target genes that participate in colon cancer progression. Recent studies identified members of the immunoglobulin-like cell adhesion molecules (IgCAM) of the L1CAM family (L1 and Nr-CAM) as targets of beta-catenin-TCF signaling in colon cancer cells. L1 was detected at the invasive front of colon cancer tissue and confers metastasis when overexpressed in cells.

L1 cell adhesion molecule (L1CAM) in invasive tumors.

The L1 cell adhesion molecule (L1CAM) belongs to the immunoglobulin superfamily and was originally identified in the nervous system. Recent studies demonstrated L1CAM expression in various types of cancer, predominantly at the invasive front of tumors and in metastases, suggesting its involvement in advanced stages of tumor progression. Overexpression of L1CAM in normal and cancer cells increased motility, enhanced growth rate and promoted cell transformation and tumorigenicity.

L1-CAM in cancerous tissues.

Background: L1-cell adhesion molecule (L1-CAM) is a cell adhesion receptor of the immunoglobulin superfamily, known for its roles in nerve cell function. While originally believed to be present only in brain cells, in recent years L1-CAM has been detected in other tissues, and in a variety of cancer cells, including some common types of human cancer.

Objective/methods: We review the prevalence of L1-CAM in human cancer, the possible mechanisms involved in L1-CAM-mediated tumorigenesis, and cancer therapies based upon L1-CAM antibody treatment.

Epithelial-mesenchymal transition and the invasive potential of tumors.

The development of metastasis requires the movement and invasion of cancer cells from the primary tumor into the surrounding tissue. To acquire such invasive abilities, epithelial cancer cells must undergo several phenotypic changes. Some of these, including alterations in cell adhesion and migration, are reminiscent of those observed during the developmental process termed epithelial-mesenchymal transition (EMT).

beta-Catenin signaling in biological control and cancer.

A coordinated integration of cell-cell adhesion and the control of gene expression is essential for the development of multicellular, differentiated organisms. beta-Catenin fulfils important regulatory functions in both cell-cell adhesion by linking cadherin adhesion receptors to the cytoskeleton, and also as a key element in the Wnt signaling pathway where it acts as cotranscriptional activator of target genes in the cell nucleus. Wnt signaling is involved in numerous aspects of embryonic development and in the control of tissue self-renewal in a variety of adult tissues.

Expression of L1-CAM and ADAM10 in human colon cancer cells induces metastasis.

L1-CAM, a neuronal cell adhesion receptor, is also expressed in a variety of cancer cells. Recent studies identified L1-CAM as a target gene of beta-catenin-T-cell factor (TCF) signaling expressed at the invasive front of human colon cancer tissue. We found that L1-CAM expression in colon cancer cells lacking L1-CAM confers metastatic capacity, and mice injected in their spleen with such cells form liver metastases.