Genomes and Genes
neural cell adhesion molecule l1
Summary: A member of the immunoglobulin superfamily of neuronal cell adhesion molecules that is required for proper nervous system development. Neural cell adhesion molecule L1 consists of six Ig domains, five fibronectin domains, a transmembrane region and an intracellular domain. Two splicing variants are known: a neuronal form that contains a four-amino acid RSLE sequence in the cytoplasmic domain, and a non-neuronal form that lacks the RSLE sequence. Mutations in the L1 gene result in L1 disease. Neural cell adhesion molecule L1 is predominantly expressed during development in neurons and Schwann cells; involved in cell adhesion, neuronal migration, axonal growth and pathfinding, and myelination.
- Gast D, Riedle S, Kiefel H, Müerköster S, Schäfer H, Schäfer M, et al. The RGD integrin binding site in human L1-CAM is important for nuclear signaling. Exp Cell Res. 2008;314:2411-8 pubmed publisher..Mutant L1 was unable to translocate to the nucleus. Our findings highlight the importance of the RGD site in L1 for human tumors and suggest that nuclear signaling of L1 is dependent on integrins. ..
- Li S, Jo Y, Lee J, Min J, Lee E, Park T, et al. L1 cell adhesion molecule is a novel independent poor prognostic factor of extrahepatic cholangiocarcinoma. Clin Cancer Res. 2009;15:7345-51 pubmed publisher..7% of ECC and its expression was significantly associated with perineural invasion. High expression of L1 and nodal metastasis were independent poor prognostic factors predicting overall survival in patients with ECC. ..
- Nakamura Y, Lee S, Haddox C, Weaver E, Lemmon V. Role of the cytoplasmic domain of the L1 cell adhesion molecule in brain development. J Comp Neurol. 2010;518:1113-32 pubmed publisher..Therefore, the L1CD is not responsible for the major defects observed in L1(KO) mice, yet it is required for continued L1 protein expression and motor function in the adult. ..
- Min J, Kim J, Li S, Lee J, Yoon H, Ryu C, et al. L1 cell adhesion molecule is a novel therapeutic target in intrahepatic cholangiocarcinoma. Clin Cancer Res. 2010;16:3571-80 pubmed publisher..We identified that L1 is expressed in ICC. L1 plays an important role in the tumor progression of ICC by enhancing cell proliferation, migration, invasion, and survival. L1 may represent a novel therapeutic target for ICC. ..
- Yeaney N, He M, Tang N, Malouf A, O Riordan M, Lemmon V, et al. Ethanol inhibits L1 cell adhesion molecule tyrosine phosphorylation and dephosphorylation and activation of pp60(src). J Neurochem. 2009;110:779-90 pubmed publisher..We conclude that ethanol disrupts L1 trafficking/signaling following its expression on the surface of the growth cone, and prior to its activation of pp60(src). ..
- Raveh S, Gavert N, Ben Ze ev A. L1 cell adhesion molecule (L1CAM) in invasive tumors. Cancer Lett. 2009;282:137-45 pubmed publisher..We review the role of L1CAM in cancer progression with particular emphasis on colon cancer, and the potential of anti-L1CAM antibodies as a therapeutic tool for cancer. ..
- Sebens Müerköster S, Werbing V, Sipos B, Debus M, Witt M, Grossmann M, et al. Drug-induced expression of the cellular adhesion molecule L1CAM confers anti-apoptotic protection and chemoresistance in pancreatic ductal adenocarcinoma cells. Oncogene. 2007;26:2759-68 pubmed..These findings substantiate our understanding of the molecular mechanisms leading to chemoresistance in PDAC cells and indicate the importance of L1CAM in this scenario. ..
- Djordjevic J, Djordjevic A, Adzic M, Radojcic M. Effects of chronic social isolation on Wistar rat behavior and brain plasticity markers. Neuropsychobiology. 2012;66:112-9 pubmed publisher..Together with our previous results, the current observations suggest that a chronic social isolation model may potentially be used to study molecular mechanisms that underlie depressive symptomatology. ..
- Choi S, Jo Y, Huang S, Liang Z, Min J, Hong H, et al. L1 cell adhesion molecule as a novel independent poor prognostic factor in gallbladder carcinoma. Hum Pathol. 2011;42:1476-83 pubmed publisher..Taken together, our findings suggest that L1 cell adhesion molecule expression could be used as a novel prognostic factor for patient survival and might be a potential therapeutic target in gallbladder carcinomas. ..
- Jakovcevski I, Mo Z, Zecevic N. Down-regulation of the axonal polysialic acid-neural cell adhesion molecule expression coincides with the onset of myelination in the human fetal forebrain. Neuroscience. 2007;149:328-37 pubmed..These results support the idea that in the human fetal forebrain axonal PSA-NCAM expression is inversely related to primary myelination. ..
- Kiefel H, Bondong S, Pfeifer M, Schirmer U, Erbe Hoffmann N, Schäfer H, et al. EMT-associated up-regulation of L1CAM provides insights into L1CAM-mediated integrin signalling and NF-?B activation. Carcinogenesis. 2012;33:1919-29 pubmed publisher..We also identify important novel downstream effector molecules of the L1CAM-integrin signalling crosstalk that help to understand the molecular mechanisms underlying L1CAM-promoted tumour progression. ..
- Bachelin C, Zujovic V, Buchet D, Mallet J, Baron van Evercooren A. Ectopic expression of polysialylated neural cell adhesion molecule in adult macaque Schwann cells promotes their migration and remyelination potential in the central nervous system. Brain. 2010;133:406-20 pubmed publisher..These results underline the potential therapeutic benefit to genetically modify Schwann cells to overcome their poor migration capacity and promote their repair potential in demyelinating disorders of the central nervous system. ..
- Lee E, Jeong M, Singh R, Jung J, Yoon H, Min J, et al. A chimeric antibody to L1 cell adhesion molecule shows therapeutic effect in an intrahepatic cholangiocarcinoma model. Exp Mol Med. 2012;44:293-302 pubmed publisher..These results suggest that the humanized A10-A3 antibody may have potential as an anticancer agent for the treatment of ICC. ..
- Marx M, Diestel S, Bozon M, Keglowich L, Drouot N, Bouché E, et al. Pathomechanistic characterization of two exonic L1CAM variants located in trans in an obligate carrier of X-linked hydrocephalus. Neurogenetics. 2012;13:49-59 pubmed publisher..The poly-ubiquitination of L1-W635C and its association with the ER chaperone calnexin provide further insights into the molecular mechanisms underlying defective cell surface trafficking of L1CAM in L1 syndrome. ..
- Winther M, Berezin V, Walmod P. NCAM2/OCAM/RNCAM: cell adhesion molecule with a role in neuronal compartmentalization. Int J Biochem Cell Biol. 2012;44:441-6 pubmed publisher..NCAM2 is primarily expressed in the brain, where it is believed to stimulate neurite outgrowth and to facilitate dendritic and axonal compartmentalization. ..
- Rawnaq T, Quaas A, Zander H, Gros S, Reichelt U, Blessmann M, et al. L1 is highly expressed in tumors of the nervous system: a study of over 8000 human tissues. J Surg Res. 2012;173:314-9 pubmed publisher..L1 thus is a potentially important therapeutic target, particularly with respect to malignant melanoma, gastrointestinal stromal tumor, neuroblastoma, and certain subtypes of non-neural tumors. ..
- Wakabayashi Y, Uchida S, Funato H, Matsubara T, Watanuki T, Otsuki K, et al. State-dependent changes in the expression levels of NCAM-140 and L1 in the peripheral blood cells of bipolar disorders, but not in the major depressive disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32:1199-205 pubmed publisher..Our results suggest that the reciprocal alteration in the expression of NCAM-140 and L1 mRNAs could be state-dependent and associated with the pathophysiology of bipolar disorder. ..
- Gavert N, Ben Shmuel A, Raveh S, Ben Ze ev A. L1-CAM in cancerous tissues. Expert Opin Biol Ther. 2008;8:1749-57 pubmed..These results, in addition to the presence of L1-CAM on the cell surface and its restricted distribution in normal tissues, make it an ideal target for tumor therapy. ..
- Kiefel H, Bondong S, Erbe Hoffmann N, Hazin J, Riedle S, Wolf J, et al. L1CAM-integrin interaction induces constitutive NF-kappaB activation in pancreatic adenocarcinoma cells by enhancing IL-1beta expression. Oncogene. 2010;29:4766-78 pubmed publisher..The unravelling of this novel mechanism sheds new light on the important role of L1CAM expression in PDAC cells. ..
- Schmid R, Maness P. L1 and NCAM adhesion molecules as signaling coreceptors in neuronal migration and process outgrowth. Curr Opin Neurobiol. 2008;18:245-50 pubmed publisher..We will also discuss how dysregulation of CAMs may also bear on neuropsychiatric disease and cancer. ..
- Castillo Gomez E, Gomez Climent M, Varea E, Guirado R, Blasco Ibáñez J, Crespo C, et al. Dopamine acting through D2 receptors modulates the expression of PSA-NCAM, a molecule related to neuronal structural plasticity, in the medial prefrontal cortex of adult rats. Exp Neurol. 2008;214:97-111 pubmed publisher
- Dou X, Menkari C, Shanmugasundararaj S, Miller K, Charness M. Two alcohol binding residues interact across a domain interface of the L1 neural cell adhesion molecule and regulate cell adhesion. J Biol Chem. 2011;286:16131-9 pubmed publisher..These findings support the hypothesis that alcohol binding within a pocket bordered by Glu-33 and Tyr-418 inhibits L1 adhesion by disrupting the Ig1-Ig4 interaction. ..
- Jung J, Son Y, Park H, Jeon S, Lee J, Choi S, et al. The cell adhesion molecule L1 promotes gallbladder carcinoma progression in vitro and in vivo. Oncol Rep. 2011;25:945-52 pubmed publisher..Taken together, these results suggest that L1 plays a crucial role in GBC progression and may be a novel therapeutic target in GBC treatment. ..
- Maheu M, Davoli M, Turecki G, Mechawar N. Amygdalar expression of proteins associated with neuroplasticity in major depression and suicide. J Psychiatr Res. 2013;47:384-90 pubmed publisher..045). These results suggest that the BLA and CeA display contrasting patterns of neuroplasticity in depression, and that greater impairment of amygdalar neuroplasticity may be associated with increased risk of suicide. ..
- Knogler K, Grünberg J, Zimmermann K, Cohrs S, Honer M, Ametamey S, et al. Copper-67 radioimmunotherapy and growth inhibition by anti-L1-cell adhesion molecule monoclonal antibodies in a therapy model of ovarian cancer metastasis. Clin Cancer Res. 2007;13:603-11 pubmed..Therapeutic data indicate, for the first time, the feasibility of combining anti-L1-directed growth inhibition and (67)Cu-radioimmunotherapy, thereby increasing the efficiency of antibody treatment of metastatic ovarian carcinoma. ..
- Zhang Y, Yeh J, Richardson P, Bo X. Cell adhesion molecules of the immunoglobulin superfamily in axonal regeneration and neural repair. Restor Neurol Neurosci. 2008;26:81-96 pubmed..This review will be focussed on the involvement of L1, NCAM, and polysialylated NCAM in neural repair and axon regeneration after nerve injury and their potential applications in the treatment of CNS injury. ..
- Parkash J, Kaur G. Potential of PSA-NCAM in neuron-glial plasticity in the adult hypothalamus: role of noradrenergic and GABAergic neurotransmitters. Brain Res Bull. 2007;74:317-28 pubmed..Further, enhanced mRNA expression of PST suggests that the biosynthesis of PSA on NCAM is regulated at the transcriptional level...
- Gavert N, Sheffer M, Raveh S, Spaderna S, Shtutman M, Brabletz T, et al. Expression of L1-CAM and ADAM10 in human colon cancer cells induces metastasis. Cancer Res. 2007;67:7703-12 pubmed..These results indicate that there is a gene program induced by L1-CAM in colon cancer cells that is also present in colorectal cancer tissue and suggest that L1-CAM can serve as target for colon cancer therapy. ..
- Ben Q, Wang J, Liu J, Zhu Y, Yuan F, Yao W, et al. Positive expression of L1-CAM is associated with perineural invasion and poor outcome in pancreatic ductal adenocarcinoma. Ann Surg Oncol. 2010;17:2213-21 pubmed publisher..Enhanced expression of L1-CAM may contribute to the pain syndrome and perineural invasion and may correlate with poor overall survival in human pancreatic cancer. ..
- Kim K, Min J, Liang Z, Lee K, Lee J, Bae K, et al. Aberrant l1 cell adhesion molecule affects tumor behavior and chemosensitivity in anaplastic thyroid carcinoma. Clin Cancer Res. 2012;18:3071-8 pubmed publisher..L1CAM plays an important role in determining tumor behavior and chemosensitivity in cell lines derived from ATCs. Therefore, we suggest that L1CAM may be an important therapeutic target in patients with ATCs. ..
- Kanemura Y, Okamoto N, Sakamoto H, Shofuda T, Kamiguchi H, Yamasaki M. Molecular mechanisms and neuroimaging criteria for severe L1 syndrome with X-linked hydrocephalus. J Neurosurg. 2006;105:403-12 pubmedMutations in the gene that codes for the human neural cell adhesion molecule L1 (L1CAM), are known to cause a wide variety of anomalies, now understood as phenotypic expressions of L1 syndrome...
- Nakakimura S, Sasaki F, Okada T, Arisue A, Cho K, Yoshino M, et al. Hirschsprung's disease, acrocallosal syndrome, and congenital hydrocephalus: report of 2 patients and literature review. J Pediatr Surg. 2008;43:E13-7 pubmed publisher..Furthermore, it is desirable to select a line treatment of HSCR to prevent infection of the ventriculoperitoneal shunt if the patient requires it. ..
- Daponte A, Kostopoulou E, Kollia P, Papamichali R, Vanakara P, Hadjichristodoulou C, et al. L1 (CAM) (CD171) in ovarian serous neoplasms. Eur J Gynaecol Oncol. 2008;29:26-30 pubmed..002). L1 (CAM) expression represents a novel diagnostic marker in serous ovarian neoplasms that shows characteristics of tumor progression. L1 expression was associated with chemotherapy response. ..
- Varea E, Guirado R, Gilabert Juan J, Martí U, Castillo Gomez E, Blasco Ibáñez J, et al. Expression of PSA-NCAM and synaptic proteins in the amygdala of psychiatric disorder patients. J Psychiatr Res. 2012;46:189-97 pubmed publisher..These results indicate that inhibitory and excitatory amygdaloid circuits are affected in these disorders and that abnormal PSA-NCAM expression in depressive and bipolar patients may underlie these alterations. ..
- Lee S, Schramme A, Doberstein K, Dummer R, Abdel Bakky M, Keller S, et al. ADAM10 is upregulated in melanoma metastasis compared with primary melanoma. J Invest Dermatol. 2010;130:763-73 pubmed publisher..Taken together, our data demonstrate that ADAM10 and L1-CAM have important roles during melanoma progression and both molecules represent attractive targets for therapeutical intervention of melanomas. ..
- Bondong S, Kiefel H, Hielscher T, Zeimet A, Zeillinger R, Pils D, et al. Prognostic significance of L1CAM in ovarian cancer and its role in constitutive NF-?B activation. Ann Oncol. 2012;23:1795-802 pubmed publisher..L1CAM expression and shedding in the tumor microenvironment could contribute to enhanced invasion and tumor progression through increased IL-1? production and NF-?B activation. ..
- Young K, Merson T, Sotthibundhu A, Coulson E, Bartlett P. p75 neurotrophin receptor expression defines a population of BDNF-responsive neurogenic precursor cells. J Neurosci. 2007;27:5146-55 pubmed
- Yoon H, Min J, Lee D, Kim D, Koh S, Hong H. L1 cell adhesion molecule and epidermal growth factor receptor activation confer cisplatin resistance in intrahepatic cholangiocarcinoma cells. Cancer Lett. 2012;316:70-6 pubmed publisher..Inhibition of EGFR activation or L1ACM greatly sensitized the cells to cisplatin. EGFR and L1CAM may be important targets for ICC therapy. ..
- Cheng L, Wu Q, Guryanova O, Huang Z, Huang Q, Rich J, et al. Elevated invasive potential of glioblastoma stem cells. Biochem Biophys Res Commun. 2011;406:643-8 pubmed publisher..Collectively, these data demonstrate the invasive nature of GSCs, suggesting that disrupting GSCs through a specific target such as L1CAM may reduce GBM cancer invasion and tumor recurrence. ..
- Geismann C, Arlt A, Bauer I, Pfeifer M, Schirmer U, Altevogt P, et al. Binding of the transcription factor Slug to the L1CAM promoter is essential for transforming growth factor-?1 (TGF-?)-induced L1CAM expression in human pancreatic ductal adenocarcinoma cells. Int J Oncol. 2011;38:257-66 pubmed..Moreover, our study is the first one describing the control of the human L1CAM promoter in tumor cells. ..
- Pfeifer M, Schirmer U, Geismann C, Schäfer H, Sebens S, Altevogt P. L1CAM expression in endometrial carcinomas is regulated by usage of two different promoter regions. BMC Mol Biol. 2010;11:64 pubmed publisher..Our findings suggest that the L1CAM transcriptional regulation is more complex than anticipated and this study provides the basis for a better understanding of L1CAM regulation in non-neuronal/tumor cells. ..
- Cui Y, Hargus G, Xu J, Schmid J, Shen Y, Glatzel M, et al. Embryonic stem cell-derived L1 overexpressing neural aggregates enhance recovery in Parkinsonian mice. Brain. 2010;133:189-204 pubmed publisher..We have generated substrate-adherent embryonic stem cell-derived neural aggregates overexpressing the neural cell adhesion molecule L1, because it has shown beneficial functions after central nervous system injury...
- Itoh K, Fujisaki K, Watanabe M. Human L1CAM carrying the missense mutations of the fibronectin-like type III domains is localized in the endoplasmic reticulum and degraded by polyubiquitylation. J Neurosci Res. 2011;89:1637-45 pubmed publisherAny mutations in the human neural cell adhesion molecule L1 (hL1CAM) gene might cause various types of serious neurological syndromes in humans, characterized by increased mortality, mental retardation, and various malformations of the ..
- Wachowiak R, Fiegel H, Kaifi J, Quaas A, Krickhahn A, Schurr P, et al. L1 is associated with favorable outcome in neuroblastomas in contrast to adult tumors. Ann Surg Oncol. 2007;14:3575-80 pubmed..This novel finding suggests an inverse role of L1 in neuroblastoma. Future studies might focus on the molecular basis of the varying effect of L1 in different tumors. ..
- Sandi C, Bisaz R. A model for the involvement of neural cell adhesion molecules in stress-related mood disorders. Neuroendocrinology. 2007;85:158-76 pubmed
- Tapanes Castillo A, Weaver E, Smith R, Kamei Y, Caspary T, Hamilton Nelson K, et al. A modifier locus on chromosome 5 contributes to L1 cell adhesion molecule X-linked hydrocephalus in mice. Neurogenetics. 2010;11:53-71 pubmed publisher..Candidate modifier loci were further investigated in an extension study. Linkage was confirmed for a locus on chromosome 5, which we named L1cam hydrocephalus modifier 1 (L1hydro1), p = 4.04 X 10(-11). ..
- Kato K, Maesawa C, Itabashi T, Fujisawa K, Otsuka K, Kanno S, et al. DNA hypomethylation at the CpG island is involved in aberrant expression of the L1 cell adhesion molecule gene in colorectal cancer. Int J Oncol. 2009;35:467-76 pubmed..These results suggest that DNA hypomethylation at the L1CAM CpG islands might induce L1CAM aberrant expression and contribute to the acquisition of aggressive tumor behavior in CRC. ..
- Gascon E, Vutskits L, Jenny B, Durbec P, Kiss J. PSA-NCAM in postnatally generated immature neurons of the olfactory bulb: a crucial role in regulating p75 expression and cell survival. Development. 2007;134:1181-90 pubmed..We propose that PSA-NCAM may promote survival by controlling the expression of the p75 receptor in developing neurons. ..
- Tsoory M, Guterman A, Richter Levin G. "Juvenile stress" alters maturation-related changes in expression of the neural cell adhesion molecule L1 in the limbic system: relevance for stress-related psychopathologies. J Neurosci Res. 2010;88:369-80 pubmed publisher..Furthermore, the findings support the "network hypothesis," which postulates that information-processing problems within relevant neural networks might underlie stress-induced mood and anxiety disorders. ..
- Nakata A, Kamiguchi H. Serine phosphorylation by casein kinase II controls endocytic L1 trafficking and axon growth. J Neurosci Res. 2007;85:723-34 pubmed..These results demonstrate the novel role of CKII in L1-mediated axon elongation and stress the importance of functional linkage between L1 phosphorylation and L1 trafficking in migrating growth cones. ..