Neural cell adhesion molecule modulates mesenchymal stromal cell migration via activation of MAPK/ERK signaling
Abstract
Mesenchymal Stromal Cells (MSCs) represent promising tools for cellular therapy owing to their multipotentiality and ability to localize to injured, inflamed sites and tumor. Various approaches to manipulate expression of MSC surface markers, including adhesion molecules and chemokine receptors, have been explored to enhance homing of MSCs. Recently, Neural Cell Adhesion Molecule (NCAM) has been found to be expressed on MSCs yet its function remains largely elusive. Herein, we show that bone marrow-derived MSCs from NCAM deficient mice exhibit defective migratory ability and significantly impaired adipogenic and osteogenic differentiation potential. We further explore the mechanism governing NCAM mediated migration of MSCs by showing the interplay between NCAM and Fibroblast Growth Factor Receptor (FGFR) induces activation of MAPK/ERK signaling, thereby the migration of MSCs. In addition, re-expression of NCAM180, but not NCAM140, could restore the defective MAPK/ERK signaling thereby the migration of NCAM deficient MSCs. Finally, we demonstrate that NCAM180 expression level could be manipulated by pro-inflammatory cytokine Tumor Necrosis Factor (TNF)-α treatment. Overall, our data reveal the vital function of NCAM in MSCs migration and differentiation thus raising the possibility of manipulating NCAM expression to enhance homing and therapeutic potential of MSCs in cellular therapy.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
CACNA1D is a neural cell adhesion molecule that contributes to cell migration via activation of MAPK/ERK signaling.
“CACNA1D is a neural cell adhesion molecule that contributes to cell migration via activation of MAPK/ERK signaling [89].”
From Self-domestication in Homo sapiens: Insights from comparative genomics (2017) · cites this paper as [89]
Cites
1 retracted
RETRACTED ARTICLE: Pluripotency of mesenchymal stem cells derived from adult marrow
Jiang, Y., Jahagirdar, B., Reinhardt, R. L., Schwartz, R. E., Keene, C. D., Ortiz-Gonzalez, X. R., Reyes, M., Lenvik, T. R., Lund, T. C., Blackstad, M., et al. (2002) · Nature · doi:10.1038/nature00870 · Cited by 5,523 · see citing works
RetractedMultilineage potential of adult human mesenchymal stem cells
Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A., Simonetti, D. W., Craig, S., & Marshak, D. R. (1999) · Science · doi:10.1126/science.284.5411.143 · Cited by 21,052 · see citing works
Human Mesenchymal Stem Cells Differentiate to a Cardiomyocyte Phenotype in the Adult Murine Heart
Toma, C., Pittenger, M. F., Cahill, K. S., Byrne, B. J., & Kessler, P. (2002) · Circulation · doi:10.1161/hc0102.101442 · Cited by 2,234 · see citing works
Bone Marrow Stromal Stem Cells: Nature, Biology, and Potential Applications
Bianco, P., Riminucci, M., Gronthos, S., & Robey, P. G. (2001) · Stem Cells · doi:10.1634/stemcells.19-3-180 · Cited by 1,944 · see citing works
Cremer, H., Lange, R., Christoph, A., Plomann, M., Vopper, G., Roes, J., Brown, R. W., Baldwin, S. A., Kraemer, P. J., Scheff, S. W., et al. (1994) · Nature · doi:10.1038/367455a0 · Cited by 1,007 · see citing works
Modulation of Akt kinase activity by binding to Hsp90
Sato, S., Fujita, N., & Tsuruo, T. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.170276797 · Cited by 967 · see citing works
Ponte, A. L., Marais, E., Gallay, N., Langonné, A., Delorme, B., Hérault, O., Charbord, P., & Domenech, J. (2007) · Stem Cells · doi:10.1634/stemcells.2007-0054 · Cited by 947 · see citing works
(2002) · PubMed · Cited by 903 · see citing works
Maness, P. F., & Schachner, M. (2006) · Nature Neuroscience · doi:10.1038/nn1827 · Cited by 850 · see citing works
Devine, S. M., Cobbs, C., Jennings, M., Bartholomew, A. M., & Hoffman, R. (2003) · Blood · doi:10.1182/blood-2002-06-1830 · Cited by 740 · see citing works
Honczarenko, M., Le, Y., Swierkowski, M., Ghiran, I., Glodek, A. M., & Silberstein, L. E. (2006) · Stem Cells · doi:10.1634/stemcells.2005-0319 · Cited by 722 · see citing works
Son, B., Marquez‐Curtis, L. A., Kucia, M., Wysoczynski, M., Turner, A. R., Ratajczak, J., Ratajczak, M. Z., & Janowska‐Wieczorek, A. (2006) · Stem Cells · doi:10.1634/stemcells.2005-0271 · Cited by 641 · see citing works
Kawada, H., Fujita, J., Kinjo, K., Matsuzaki, Y., Tsuma, M., Miyatake, H., Muguruma, Y., Tsuboi, K., Itabashi, Y., Ikeda, Y., et al. (2004) · Blood · doi:10.1182/blood-2004-04-1488 · Cited by 566 · see citing works
Mesenchymal stem cells display coordinated rolling and adhesion behavior on endothelial cells
Rüster, B., Göttig, S., Ludwig, R. J., Bistrian, R., Müller, S., Seifried, E., Gille, J., & Henschler, R. (2006) · Blood · doi:10.1182/blood-2006-05-025098 · Cited by 562 · see citing works
Chapel, A., Bertho, J., Bensidhoum, M., Fouillard, L., Young, R. G., Frick, J., Demarquay, C., Cuvelier, F., Mathieu, E., Trompier, F., et al. (2003) · The Journal of Gene Medicine · doi:10.1002/jgm.452 · Cited by 460 · see citing works
Ji, J. F., He, B. P., Dheen, S. T., & Tay, S. S. W. (2004) · Stem Cells · doi:10.1634/stemcells.22-3-415 · Cited by 443 · see citing works
Forte, G., Minieri, M., Cossa, P., Antenucci, D., Sala, M., Gnocchi, V. F., Fiaccavento, R., Carotenuto, F., Vito, P. D., Baldini, P. M., et al. (2005) · Stem Cells · doi:10.1634/stemcells.2004-0176 · Cited by 401 · see citing works
Kolkova, K., Novitskaya, V., Pedersen, N. M., Berezin, V., & Bock, E. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-06-02238.2000 · Cited by 330 · see citing works
Multipotential Mesenchymal Stem Cells Are Mobilized into Peripheral Blood by Hypoxia
Rochefort, G. Y., Delorme, B., López, A., Hérault, O., Bonnet, P., Charbord, P., Eder, V., & Domenech, J. (2006) · Stem Cells · doi:10.1634/stemcells.2006-0164 · Cited by 315 · see citing works
Concise Review: Multipotent Mesenchymal Stromal Cells in Blood
He, Q., Wan, C., & Li, G. (2006) · Stem Cells · doi:10.1634/stemcells.2006-0335 · Cited by 284 · see citing works
Neural recognition molecules and synaptic plasticity
Schachner, M. (1997) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(97)80115-9 · Cited by 284 · see citing works
NCAM140 Interacts with the Focal Adhesion Kinase p125 and the SRC-related Tyrosine Kinase p59
Beggs, H. E., Baragona, S. C., Hemperly, J. J., & Maness, P. F. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.13.8310 · Cited by 280 · see citing works
Tamama, K., Fan, V. H., Griffith, L. G., Blair, H. C., & Wells, A. H. (2005) · Stem Cells · doi:10.1634/stemcells.2005-0176 · Cited by 256 · see citing works
Wang, L., Li, Y., Chen, X., Chen, J., Gautam, S. C., Xu, Y., & Chopp, M. (2002) · Hematology · doi:10.1080/10245330290028588 · Cited by 241 · see citing works
Self-citationMenon, L. G., Picinich, S. C., Koneru, R., Gao, H., Lin, S. Y., Koneru, M., Mayer‐Kuckuk, P., Glod, J. W., & Banerjee, D. (2006) · Stem Cells · doi:10.1634/stemcells.2006-0257 · Cited by 237 · see citing works
Bixby, J. L., Pratt, R. S., Lilien, J. E., & Reichardt, L. F. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.8.2555 · Cited by 231 · see citing works
The neural cell adhesion molecule in synaptic plasticity and ageing
Rønn, L. C. B., Berezin, V., & Bock, E. (2000) · International Journal of Developmental Neuroscience · doi:10.1016/s0736-5748(99)00088-x · Cited by 213 · see citing works
Gao, H., Priebe, W., Glod, J. W., & Banerjee, D. (2009) · Stem Cells · doi:10.1002/stem.23 · Cited by 202 · see citing works
The neural cell adhesion molecule (NCAM) in development and plasticity of the nervous system
Rønn, L. C. B., Hartz, B. P., & Bock, E. (1998) · Experimental Gerontology · doi:10.1016/s0531-5565(98)00040-0 · Cited by 198 · see citing works
NCAM‐induced focal adhesion assembly: a functional switch upon loss of E‐cadherin
Lehembre, F., Yilmaz, M., WICKI, A. N., Schomber, T., Strittmatter, K., Ziegler, D., Kren, A., Went, P., Derksen, P. W. B., Berns, A. J. M., et al. (2008) · The EMBO Journal · doi:10.1038/emboj.2008.178 · Cited by 194 · see citing works
Actin dynamics and turnover in cell motility
Rottner, K., & Stradal, T. E. B. (2011) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2011.07.003 · Cited by 190 · see citing works
Migration of Mesenchymal Stem Cells Through Cerebrospinal Fluid into Injured Spinal Cord Tissue
Satake, K., Lou, J., & Lenke, L. G. (2004) · Spine · doi:10.1097/01.brs.0000138273.02820.0a · Cited by 186 · see citing works
NCAM‐induced intracellular signaling revisited
Ditlevsen, D. K., Povlsen, G. K., Berezin, V., et al. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21551 · Cited by 167 · see citing works
Multitasking in Tumor Progression: Signaling Functions of Cell Adhesion Molecules
Cavallaro, U., & Christofori, G. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1294.006 · Cited by 159 · see citing works
Hemeda, H., Jakob, M., Ludwig, A., Giebel, B., Lang, S., & Brandau, S. (2010) · Stem Cells and Development · doi:10.1089/scd.2009.0365 · Cited by 158 · see citing works
Wnt Signaling Regulates the Invasion Capacity of Human Mesenchymal Stem Cells
Neth, P., Karow, M., Egea, V., Hoelters, J., Jochum, M., & Ries, C. (2006) · Stem Cells · doi:10.1634/stemcells.2005-0503 · Cited by 151 · see citing works
Ryu, C. H., Park, S. A., Kim, S. M., et al. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.06.043 · Cited by 149 · see citing works
Ditlevsen, D. K., Køhler, L. B., Pedersen, M. V., Risell, M., Kolkova, K., Meyer, M., Berezin, V., & Bock, E. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01538.x · Cited by 134 · see citing works
Bhakta, S., Hong, P., & Koç, O. N. (2006) · Cardiovascular revascularization medicine · doi:10.1016/j.carrev.2005.10.008 · Cited by 134 · see citing works
Prag, S., Lepekhin, E. A., Kolkova, K., Hartmann‐Petersen, R., Kawa, A., Walmod, P. S., Belman, V., Gallagher, H. C., Berezin, V., Bock, E., et al. (2002) · Journal of Cell Science · doi:10.1242/jcs.115.2.283 · Cited by 114 · see citing works
Croitoru‐Lamoury, J., Lamoury, F. M. J., Zaunders, J. J., Veas, L. A., & Brew, B. J. (2007) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2006.0037 · Cited by 113 · see citing works
Fu, X., Han, B., Cai, S., Lei, Y., Sun, T., & Sheng, Z.-Y. (2009) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2009.00454.x · Cited by 104 · see citing works
Krushel, L. A., Tai, M.-H., Cunningham, B. A., Edelman, G. M., & Crossin, K. L. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.5.2592 · Cited by 93 · see citing works
Jessen, U., Novitskaya, V., Pedersen, N. M., et al. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00636.x · Cited by 86 · see citing works
Mériane, M., Duhamel, S., Lejeune, L., et al. (2006) · Stem Cells · doi:10.1634/stemcells.2006-0209 · Cited by 78 · see citing works
Neural Cell Adhesion Molecule in Cancer: Expression and Mechanisms
Zecchini, S., & Cavallaro, U. (2009) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-1170-4_20 · Cited by 47 · see citing works
Olofsson, C. S., Håkansson, J., Salehi, A. A., Bengtsson, M., Galvanovskis, J., Partridge, C., Sörhede‐Winzell, M., Xian, X., Eliasson, L., Lundquist, I., et al. (2009) · Endocrinology · doi:10.1210/en.2008-0475 · Cited by 42 · see citing works
Han, T. M., & Vries, G. J. D. (1999) · Journal of Neurobiology · doi:10.1002/(sici)1097-4695(199903)38:4 · Cited by 35 · see citing works
Vargas, F., Tolosa, F. R., Sospedra, M., et al. (1994) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.1994.tb05516.x · Cited by 33 · see citing works
Yang, H. J., Xia, Y. Y., Wang, L., Liu, R., Goh, K. J., Ju, P. J., & Feng, Z. W. (2011) · Journal of Cell Science · doi:10.1242/jcs.085340 · Cited by 31 · see citing works
Self-citationNeural Cell Adhesion Molecule Contributes to Hemopoiesis‐Supporting Capacity of Stromal Cell Lines
Wang, X., Hisha, H., Taketani, S., Inaba, M., Li, Q., Cui, W., Song, C., Fan, T., Cui, Y., Guo, K., et al. (2005) · Stem Cells · doi:10.1634/stemcells.2004-0343 · Cited by 30 · see citing works
Zocchi, M. R., Vidal, M., & Poggi, A. D. (1993) · Experimental Cell Research · doi:10.1006/excr.1993.1017 · Cited by 30 · see citing works
Shi, Y., Liu, R., Zhang, S., et al. (2011) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2011.01.016 · Cited by 24 · see citing works
Self-citationWang, L., Hisha, H., Mizokami, T., et al. (2009) · Haematologica · doi:10.3324/haematol.2009.013151 · Cited by 24 · see citing works
Self-citationContribution of neural cell adhesion molecule (NCAM) to hemopoietic system in monkeys
Kato, J., Hisha, H., Wang, X., Mizokami, T., Okazaki, S., Li, Q., Song, C., Maki, M., Hosaka, N., Adachi, Y., et al. (2008) · Annals of Hematology · doi:10.1007/s00277-008-0513-9 · Cited by 20 · see citing works
Liu, R., Shi, Y., Yang, H. J., Wang, L., Zhang, S., Xia, Y. Y., Wong, J. L. J., & Feng, Z. W. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.237297 · Cited by 17 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Self-domestication in Homo sapiens: Insights from comparative genomics
Theofanopoulou, C., Gastaldon, S., O’Rourke, T., Samuels, B. D., Messner, A., Martins, P. T., Delogu, F., Alamri, S., & Boeckx, C. (2017) · PLOS ONE · doi:10.1371/journal.pone.0185306 · Cited by 174 · see citing works
- Authors
- Shi, Y., Xia, Y.-Y., Wang, L., Liu, R., Khoo, K.-S., & Feng, Z.-W.
- Affiliations
- Nanyang Technological University (SG)
- Xi'an Jiaotong University (CN)
- MSD (Singapore) (SG)
- Venue
- Experimental Cell Research
- Publisher
- Elsevier BV
- Published
- 2012-10
- Volume
- 318
- Issue
- 17
- Pages
- 2257-2267
- ISSN
- 0014-4827 (ISSN-L)
- OpenAlex
- W2029576388
- Cited by
- 45
- References
- 56
- Citations by year
- 2026: 3 · 2024: 5 · 2023: 5 · 2022: 4 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 4 · 2016: 6 · 2015: 1 · 2014: 3 · 2013: 5 · 2012: 1
- FWCI
- 1.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Experimental Cell Research (publishedVersion)
- PubMed (publishedVersion)
- DR-NTU (Nanyang Technological University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- CD56, mesenchymal stem cells, cell migration, ERK signaling, fibroblast growth factor receptor, adipogenesis, osteogenic differentiation, TNF-α, cell homing, bone marrow-derived stromal cells, cell therapy
- MeSH terms
- Animals, Cell Adhesion, Cell Differentiation, Cell Movement, Female, Flow Cytometry, Immunoenzyme Techniques, Male, Mice, Inbred C57BL, Osteogenesis, Phosphorylation, RNA, Messenger, Tumor Necrosis Factor-alpha, Blotting, Western, Receptors, Fibroblast Growth Factor, Adipocytes, Mice, Knockout, CD56 Antigen, Reverse Transcriptase Polymerase Chain Reaction, MAP Kinase Signaling System, Extracellular Signal-Regulated MAP Kinases, Mice, Mesenchymal Stem Cells, Real-Time Polymerase Chain Reaction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
