Neural Cell Adhesion Molecule in Cancer: Expression and Mechanisms

Zecchini, Silvia; Cavallaro, Ugo

doi:10.1007/978-1-4419-1170-4_20

Cited by 34 publications

(21 citation statements)

References 66 publications

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“…NCAM is strongly upregulated in many neuroblastomas, where it becomes post-translationally modified to PSA-NCAM, thus enhancing invasion of tumor cells [40]. Overexpression of L1 correlates with tumor progression and metastasis in certain neural tumors, most notably melanoma [41], while NrCAM is upregulated in high risk neuroblastomas without N-myc amplification [42].…”

Section: Neural Adhesion Molecules and Cancermentioning

confidence: 99%

L1 and NCAM adhesion molecules as signaling coreceptors in neuronal migration and process outgrowth

Schmid

Maness

2008

Current Opinion in Neurobiology

199

169

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Summary of Recent AdvancesNeural cell adhesion molecules (CAMs) of the immunoglobulin superfamily engage in multiple neuronal interactions that influence cell migration, axonal and dendritic projection, and synaptic targeting. Their downstream signal transduction events specify whether a cell moves or projects axons and dendrites to targets in the brain. Many of the diverse functions of CAMs are brought about through homophilic and heterophilic interactions with other cell surface receptors. An emerging concept is that CAMs act as co-receptors to assist in intracellular signal transduction, and to provide cytoskeletal linkage necessary for cell and growth cone motility. Here we will focus on new discoveries that have revealed novel co-receptor functions for the best understood CAMs -L1, CHL1, and NCAM-important for neuronal migration and axon guidance. We will also discuss how dysregulation of CAMs may also bear on neuropsychiatric disease and cancer.

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Section: Neural Adhesion Molecules and Cancermentioning

confidence: 99%

L1 and NCAM adhesion molecules as signaling coreceptors in neuronal migration and process outgrowth

Schmid

Maness

2008

Current Opinion in Neurobiology

199

169

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“…CASPR2 overexpression does not affect migration and invasion Cell adhesion molecules, like neural cell adhesion molecule, are thought to have a role in invasiveness and progression in cancer (Zecchini and Cavallaro, 2010). As CASPR2 also functions as a cell adhesion molecule, we determined whether CASPR2 expression may affect cell migration and invasion.…”

Section: Caspr2 Overexpression Decreases the Proliferation Ratementioning

confidence: 99%

The CASPR2 cell adhesion molecule functions as a tumor suppressor gene in glioma

et al. 2010

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Genomic translocations have been implicated in cancer.In this study, we performed a screen for genetic translocations in gliomas based on exon-level expression profiles. We identified a translocation in the contactinassociated protein-like 2 (CASPR2) gene, encoding a cell adhesion molecule. CASPR2 mRNA was fused to an expressed sequence tag that likely is part of the nuclear receptor coactivator 1 gene. Despite high mRNA expression levels, no CASPR2 fusion protein was detected. In a set of 25 glioblastomas and 22 oligodendrogliomas, mutation analysis identified two additional samples with genetic alterations in the CASPR2 gene and all three identified genetic alterations are likely to reduce CASPR2 protein expression levels. Methylation of the CASPR2 gene was also observed in gliomas and glioma cell lines. CASPR2-overexpressing cells showed decreased proliferation rates, likely because of an increase in apoptosis. Moreover, high CASPR2 mRNA expression level is positively correlated with survival and is an independent prognostic factor. These results indicate that CASPR2 acts as a tumor suppressor gene in glioma.

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“…Previous studies revealed the important role of cell surface molecules on the progression of melanoma (55). NCAM was shown to participate in the progression of various tumors with different effects (10). We pioneered the study previously that NCAM potentiates the cellular invasion and metastasis of melanoma (17).…”

Section: Discussionmentioning

confidence: 99%

“…Neural cell adhesion molecule (NCAM), 2 a member of the immunoglobulin superfamily, has been well characterized in cell proliferation, differentiation, migration, neurite outgrowth, and synaptic plasticity in the nervous system (6 -9). However, recent studies have also revealed that the expression of NCAM drastically fluctuates in many tumors and affects tumor progression and prognosis (10). In small cell lung cancer (11) and the majority of multiple myelomas (12), the up-regulation of NCAM was shown to associate with a more aggressive tumor phenotype and poor prognosis.…”

mentioning

confidence: 99%

Neural Cell Adhesion Molecule Potentiates the Growth of Murine Melanoma via β-Catenin Signaling by Association with Fibroblast Growth Factor Receptor and Glycogen Synthase Kinase-3β

Shi

Yang

et al. 2011

Journal of Biological Chemistry

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The neural cell adhesion molecule (NCAM) was recently shown to be involved in the progression of various tumors with diverse effects. We previously demonstrated that NCAM potentiates the cellular invasion and metastasis of melanoma. Here we further report that the growth of melanoma is obviously retarded when the expression of NCAM is silenced. We found that the proliferation of murine B16F0 melanoma cells, their colony formation on soft agar, and growth of transplanted melanoma in vivo are clearly inhibited by the introduction of NCAM siRNA. Interestingly, change of NCAM expression level is shown to regulate the activity of Wnt signaling molecule, ␤-catenin, markedly. This novel machinery requires the function of FGF receptor and glycogen synthase kinase-3␤ but is independent of the Wnt receptors, MAPK-Erk and PI3K/Akt pathways. In addition, NCAM is found to form a functional complex with ␤-catenin, FGF receptor, and glycogen synthase kinase-3␤. Moreover, up-regulation of NCAM140 and NCAM180 appears more potent than NCAM120 in activation of ␤-catenin, suggesting that the intracellular domain of NCAM is required for facilitating the ␤-catenin signaling. Furthermore, the melanoma cells also exhibit distinct differentiation phenotypes with the NCAM silencing. Our findings reveal a novel regulatory role of NCAM in the progression of melanoma that might serve as a new therapeutic target for the treatment of melanoma.Melanoma arises from skin neural crest-derived pigmented melanocytes and accounts for around 80% of mortality of skin cancer (1) with less than 5% of a 5-year survival rate (2). The rapid growth of melanoma cells by overriding senescence and activation of pro-proliferating signal transduction were shown to play a key role in the development of melanoma into metastatic stage (3). Even though many cell growth promoting factors have been identified to be involved in the progression of melanoma and targeted for therapeutic intervention, the treatment efficacy of advanced melanoma with vertical growth and metastasis has not been significantly improved over the past few decades (1). Hence, further study to elucidate the molecular mechanisms underlying the proliferation of melanoma cells is required for the finding of novel potential intervention targets to improve the treatment of melanoma.It has been demonstrated that the adhesion molecules that mediate intercellular and cell-matrix interactions extensively participate in the progression of melanoma (4, 5) by altering the adhesion status and signal transduction of the cells. Neural cell adhesion molecule (NCAM), 2 a member of the immunoglobulin superfamily, has been well characterized in cell proliferation, differentiation, migration, neurite outgrowth, and synaptic plasticity in the nervous system (6 -9). However, recent studies have also revealed that the expression of NCAM drastically fluctuates in many tumors and affects tumor progression and prognosis (10). In small cell lung cancer (11) and the majority of multiple myelomas (12), the up-regulation of NC...

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Neural Cell Adhesion Molecule in Cancer: Expression and Mechanisms

Cited by 34 publications

References 66 publications

L1 and NCAM adhesion molecules as signaling coreceptors in neuronal migration and process outgrowth

L1 and NCAM adhesion molecules as signaling coreceptors in neuronal migration and process outgrowth

The CASPR2 cell adhesion molecule functions as a tumor suppressor gene in glioma

Neural Cell Adhesion Molecule Potentiates the Growth of Murine Melanoma via β-Catenin Signaling by Association with Fibroblast Growth Factor Receptor and Glycogen Synthase Kinase-3β

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