The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Netrin-1 expression confers a selective advantage for tumor cell survival in metastatic breast cancer
Open accessAbstract
Netrin-1, an axon navigation cue was proposed to play a crucial role during colorectal tumorigenesis by regulating apoptosis. The netrin-1 receptors DCC and UNC5H were shown to belong to the family of dependence receptors that share the ability to induce apoptosis in the absence of their ligands. Such a trait confers on these receptors a tumor suppressor activity. Expression of one of these dependence receptors at the surface of a tumor cell is indeed speculated to render this cell dependent on ligand availability for its survival, hence inhibiting uncontrolled cell proliferation or metastasis. Consequently, it is a selective advantage for a tumor cell to lose this dependence receptor activity, as previously described with losses of DCC and UNC5H expression in human cancers. However, the model predicts that a similar advantage may be obtained by gaining autocrine expression of the ligand. We describe here that, unlike human nonmetastatic breast tumors, a large fraction of metastatic breast cancers overexpress netrin-1. Moreover, we show that netrin-1-expressing mammary metastatic tumor cell lines undergo apoptosis when netrin-1 expression is experimentally decreased or when decoy soluble receptor ectodomains are added. Such treatments prevent metastasis formation both in a syngenic mouse model of lung colonization of a mammary cancer cell line and in a model of spontaneous lung metastasis of xenografted human breast tumor. Thus, netrin-1 expression observed in a large fraction of human metastatic breast tumors confers a selective advantage for tumor cell survival and potentially represents a promising target for alternative anticancer therapeutic strategies.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
In the citing paper
“(1) upregulating the expression of their cognate ligands such as NTN1 [360–362]”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [360]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
Hong, K., Hinck, L., Nishiyama, M., Poo, M.-M., Tessier‐Lavigne, M., & Stein, E. (1999) · Cell · doi:10.1016/s0092-8674(00)80804-1 · Cited by 684
RetractedGene expression profiling predicts clinical outcome of breast cancer
van 't Veer, L. J., Dai, H., van de Vijver, M. J., He, Y. D., Hart, A. A. M., Mao, M., Peterse, H. L., van der Kooy, K., Marton, M. J., Witteveen, A. T., et al. (2002) · Nature · doi:10.1038/415530a · Cited by 9,536
Involvement of chemokine receptors in breast cancer metastasis
Müller, A., Homey, B., Soto, H., Ge, N., Catron, D., Buchanan, M. E., McClanahan, T., Murphy, E., Yuan, W., Wagner, S. N., et al. (2001) · Nature · doi:10.1038/35065016 · Cited by 5,340
Lessons from hereditary colorectal cancer
Kinzler, K. W., & Vogelstein, B. (1996) · Cell · doi:10.1016/s0092-8674(00)81333-1 · Cited by 4,919
Identification of a Chromosome 18q Gene that Is Altered in Colorectal Cancers
Fearon, E. R., Cho, K. R., Nigro, J. M., Kern, S. E., Simons, J. W., Ruppert, J. M., Hamilton, S. R., Preisinger, A. C., Thomas, G., Kinzler, K. W., et al. (1990) · Science · doi:10.1126/science.2294591 · Cited by 1,760
The netrins define a family of axon outgrowth-promoting proteins homologous to C. elegans UNC-6.
Serafini, T., Kennedy, T. E., Gaiko, M. J., Mirzayan, C., Jessell, T., & Tessier-Lavigne, M. (1994) · Cell · doi:10.1016/0092-8674(94)90420-0 · Cited by 1,397
Netrin-1 is required for commissural axon guidance in the developing vertebrate nervous system.
Serafini, T., Colamarino, S., Leonardo, E., Wang, H., Beddington, R., Skarnes, W., & Tessier-Lavigne, M. (1996) · Cell · doi:10.1016/s0092-8674(00)81795-x · Cited by 1,328
Aslakson, C. J., & Miller, F. R. (1992) · PubMed · Cited by 1,234
Deleted in Colorectal Cancer (DCC) encodes a netrin receptor.
Keino-Masu, K., Masu, M., Hinck, L., Leonardo, E., Chan, S., Culotti, J., & Tessier-Lavigne, M. (1996) · Cell · doi:10.1016/s0092-8674(00)81336-7 · Cited by 1,048
de Kok, J. B., Roelofs, R., Giesendorf, B. A. J., Pennings, J. L. A., Waas, E. T., Feuth, T. B., Swinkels, D. W., & Span, P. N. (2004) · Laboratory Investigation · doi:10.1038/labinvest.3700208 · Cited by 580
The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system
Lu, X., le Noble, F. A. C., Li, Y., Jiang, Q., de Lafarge, B., Sugiyama, D., Bréant, C., Claes, F., Smet, F. D., Thomas, J., et al. (2004) · Nature · doi:10.1038/nature03080 · Cited by 550
The DCC gene product induces apoptosis by a mechanism requiring receptor proteolysis
Mehlen, P., Rabizadeh, S., Snipas, S. J., Assa‐Munt, N., Salvesen, G. S., & Bredesen, D. E. (1998) · Nature · doi:10.1038/27441 · Cited by 437
Self-citationDAP kinase links the control of apoptosis to metastasis
Inbal, B., Cohen, O., Polak‐Charcon, S., Kopolovic, J., Vadai, E., Eisenbach, L., & Kimchi, A. (1997) · Nature · doi:10.1038/36599 · Cited by 399
Breast Cancer With Synchronous Metastases: Trends in Survival During a 14-Year Period
André, F., Slimane, K., Bachelot, T., Dunant, A., Namer, M., Barrelier, A., Kabbaj, O., Spano, J., Marsiglia, H. R., Rouzier, R., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.08.095 · Cited by 391
Self-citationNetrins Promote Developmental and Therapeutic Angiogenesis
Wilson, B. D., Ii, M., Park, K. W., Suli, A., Sorensen, L. K., Larrieu-Lahargue, F., Urness, L. D., Suh, W., Asai, J., Kock, G. A. H., et al. (2006) · Science · doi:10.1126/science.1124704 · Cited by 369
The mouse rostral cerebellar malformation gene encodes an UNC-5-like protein
Ackerman, S. L., Kozak, L. P., Przyborski, S. A., Rund, L. A., Boyer, B. B., & Knowles, B. B. (1997) · Nature · doi:10.1038/386838a0 · Cited by 367
The axonal attractant Netrin-1 is an angiogenic factor
Park, K. W., Crouse, D., Lee, M., Karnik, S. K., Sorensen, L. K., Murphy, K. J., Kuo, C. J., & Li, D. Y. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405984101 · Cited by 355
Netrin‐1 acts as a survival factor via its receptors UNC5H and DCC
Llambi, F., Causeret, F., Bloch‐Gallego, E., & Mehlen, P. (2001) · The EMBO Journal · doi:10.1093/emboj/20.11.2715 · Cited by 349
Self-citationNetrin-1 controls colorectal tumorigenesis by regulating apoptosis
Mazelin, L., Bernet, A., Bonod‐Bidaud, C., Pays, L., Arnaud, S., Gespach, C. P., Bredesen, D. E., Scoazec, J., & Mehlen, P. (2004) · Nature · doi:10.1038/nature02788 · Cited by 338
Self-citationNetrin-1-mediated axon outgrowth requires deleted in colorectal cancer-dependent MAPK activation
Forcet, C., Stein, E., Pays, L., Corset, V., Llambi, F., Tessier‐Lavigne, M., & Mehlen, P. (2002) · Nature · doi:10.1038/nature748 · Cited by 273
Self-citationSrinivasan, K., Strickland, P. A., Valdes, A. M., Shin, G. C., & Hinck, L. (2003) · Developmental Cell · doi:10.1016/s1534-5807(03)00054-6 · Cited by 263
Activation of the UNC5B receptor by Netrin-1 inhibits sprouting angiogenesisPreprint
Larrivée, B., Freitas, C., Trombe, M., Lv, X., DeLafarge, B., Li, Y., Bouvrée, K., Bréant, C., Toro, R. D., Bréchot, N., et al. (2007) · Genes & Development · doi:10.1101/gad.437807 · Cited by 257
Yebra, M., Montgomery, A. M. P., Diaferia, G. R., Kaido, T. J., Silletti, S., Perez, B., Just, M. L., Hildbrand, S., Rosemary, H., Florkiewicz, E., et al. (2003) · Developmental Cell · doi:10.1016/s1534-5807(03)00330-7 · Cited by 229
The netrin-1 receptors UNC5H are putative tumor suppressors controlling cell death commitment
Thiébault, K., Mazelin, L., Pays, L., Llambi, F., Joly, M., Scoazec, J., Saurin, J., Romeo, G., & Mehlen, P. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0738063100 · Cited by 202
Self-citationNovel Role for Netrins in Regulating Epithelial Behavior during Lung Branching Morphogenesis
Liu, Y., Stein, E., Oliver, T. N., Li, Y. H., Brunken, W. J., Koch, M., Tessier‐Lavigne, M., & Hogan, B. L. M. (2004) · Current Biology · doi:10.1016/j.cub.2004.05.020 · Cited by 192
The dependence receptor UNC5H2 mediates apoptosis through DAP‐kinase
Llambi, F., Lourenço, F. C., Gozuacik, D., Guix, C., Pays, L., Del Rio, G., Kimchi, A., & Mehlen, P. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600584 · Cited by 173
Self-citationNetrin-1 induces angiogenesis via a DCC-dependent ERK1/2-eNOS feed-forward mechanism
Nguyen, A., & Cai, H. “. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0511011103 · Cited by 169
Bernet, A., Mazelin, L., Coissieux, M., Gadot, N., Ackerman, S. L., Scoazec, J., & Mehlen, P. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.08.009 · Cited by 155
Self-citationRole of the Dependence Receptor DCC in Colorectal Cancer Pathogenesis
Mehlen, P., & Fearon, E. R. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.02.019 · Cited by 154
Self-citationQuantification of expression of netrins, slits and their receptors in human prostate tumors
Latil, A., Chêne, L., Cochand‐Priollet, B., Mangin, P., Fournier, G., Berthon, P., & Cussenot, O. (2002) · International Journal of Cancer · doi:10.1002/ijc.10821 · Cited by 148
Epigenetic and Genetic Alterations in Netrin-1 Receptors UNC5C and DCC in Human Colon Cancer
Shin, S. K., Nagasaka, T., Jung, B. H., Matsubara, N., Kim, W. H., Carethers, J. M., Boland, C. R., & Goel, A. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.08.074 · Cited by 124
Netrin Binds Discrete Subdomains of DCC and UNC5 and Mediates Interactions between DCC and Heparin
Geisbrecht, B. V., Dowd, K. A., Barfield, R. W., Longo, P. A., & Leahy, D. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302943200 · Cited by 120
Tauszig-Delamasure, S., Yu, L.-Y., Cabrera, J. R., Bouzas-Rodríguez, J., Mermet-Bouvier, C., Guix, C., Bordeaux, M.-C., Arumäe, U., & Mehlen, P. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701243104 · Cited by 107
Self-citationReceptors that mediate cellular dependence
Bredesen, D. E., Mehlen, P., & Rabizadeh, S. (2005) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401680 · Cited by 100
Self-citationDependence receptors: between life and death
Mehlen, P., & Thibert, C. (2004) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-004-3467-7 · Cited by 76
Self-citationMaking the Case for DCC and UNC5C as Tumor-Suppressor Genes in the Colon
Grady, W. M. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.10.034 · Cited by 45
Cited by
Sorted by citations
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680
van Gils, J. M., Derby, M. C., Fernandes, L. R., Ramkhelawon, B., Ray, T. D., Rayner, K. J., Parathath, S., Distel, E., Feig, J. L., Alvarez-Leite, J. I., et al. (2012) · Nature Immunology · doi:10.1038/ni.2205 · Cited by 365
Cancer-Associated Neurogenesis and Nerve-Cancer Cross-talk
Silverman, D. A., Martinez, V. K., Dougherty, P. M., Myers, J. N., Călin, G. A., & Amit, M. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-2793 · Cited by 304
Novel roles for Slits and netrins: axon guidance cues as anticancer targets?
Mehlen, P., Delloye‐Bourgeois, C., & Chédotal, A. (2011) · Nature reviews. Cancer · doi:10.1038/nrc3005 · Cited by 301
Self-citationNetrin-1 promotes adipose tissue macrophage retention and insulin resistance in obesity
Ramkhelawon, B., Hennessy, E. J., Ménager, M. M., Ray, T. D., Sheedy, F. J., Hutchison, S. B., Wanschel, A. C. B. A., Oldebeken, S. R., Geoffrion, M., Spiro, W., et al. (2014) · Nature Medicine · doi:10.1038/nm.3467 · Cited by 280
Metadata
- Authors
- Fitamant, J., Guenebeaud, C., Coissieux, M.-M., Guix, C., Treilleux, I., Scoazec, J.-Y., Bachelot, T., Bernet, A., & Mehlen, P.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Lyon 1 Université (FR)
- Corresponding author
- Mehlen, Patrick
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-03-25
- Volume
- 105
- Issue
- 12
- Pages
- 4850-4855
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2290782
- OpenAlex
- W1980116118
- Cited by
- 241
- References
- 36
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 12 · 2023: 12 · 2022: 18 · 2021: 10 · 2020: 16 · 2019: 15 · 2018: 17 · 2017: 13 · 2016: 13 · 2015: 11 · 2014: 14 · 2013: 15 · 2012: 13
- FWCI
- 6.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Commission
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Ligue Contre le Cancer
- Centre National de la Recherche Scientifique
- Institut National Du Cancer
- Université de Lyon
- Goddard Space Flight Center
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- netrin-1, metastatic breast cancer, dependence receptors, DCC receptor, apoptosis, tumor cell survival, lung metastasis, tumor suppressor activity, cancer therapy targets
- MeSH terms
- Netrin-1, Animals, Breast Neoplasms, Cell Survival, Female, Humans, Lung Neoplasms, Neoplasm Metastasis, Neoplasm Transplantation, Nerve Growth Factors, Biomarkers, Tumor, Gene Expression Regulation, Neoplastic, Cell Death, Autocrine Communication, Reverse Transcriptase Polymerase Chain Reaction, Tumor Suppressor Proteins, Cell Line, Tumor, Mice
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
