Yes and PI3K Bind CD95 to Signal Invasion of Glioblastoma
Open accessAbstract
Invasion of surrounding brain tissue by isolated tumor cells represents one of the main obstacles to a curative therapy of glioblastoma multiforme. Here we unravel a mechanism regulating glioma infiltration. Tumor interaction with the surrounding brain tissue induces CD95 Ligand expression. Binding of CD95 Ligand to CD95 on glioblastoma cells recruits the Src family member Yes and the p85 subunit of phosphatidylinositol 3-kinase to CD95, which signal invasion via the glycogen synthase kinase 3-beta pathway and subsequent expression of matrix metalloproteinases. In a murine syngeneic model of intracranial GBM, neutralization of CD95 activity dramatically reduced the number of invading cells. Our results uncover CD95 as an activator of PI3K and, most importantly, as a crucial trigger of basal invasion of glioblastoma in vivo.
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?
GOF mut-p53 has been shown to abnormally regulate a multitude of genes that play critical roles in glioblastoma pathogenesis, including CD95/Fas/Apo1, PARP, PTEN, and more.
“Furthermore, GOF mut-p53 has been shown to abnormally regulate a multitude of genes that play critical roles in GBM pathogenesis, but have not been analyzed in the context of GBM. This includes CD95/Fas/Apo1, PARP, PTEN, and more [63,94,95,96,97,98].”
From The p53 Pathway in Glioblastoma (2018) · cites this paper as [95]
Cites
Boldin, M. P., Varfolomeev, E. E., Pancer, Z., Mett, I. L., Camonis, J. H., & Wallach, D. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.14.7795 · Cited by 993 · see citing works
Control of neuronal branching by the death receptor CD95 (Fas/Apo-1)
Zuliani, C., Kleber, S., Klussmann, S., Wenger, T., Kenzelmann, M., Schreglmann, N., Martinez, A., del Rio, J. A., Soriano, E., Vodrazka, P., et al. (2006) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401720 · Cited by 117 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The p53 Pathway in Glioblastoma
Zhang, Y., Dube, C., Gibert, M., Cruickshanks, N., Wang, B., Coughlan, M., Yang, Y., Setiady, I., Deveau, C., Saoud, K., et al. (2018) · Cancers · doi:10.3390/cancers10090297 · Cited by 440 · see citing works
NKG2D: A Master Regulator of Immune Cell Responsiveness
Wensveen, F. M., Jelenčić, V., & Polić, B. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00441 · Cited by 271 · see citing works
T cells genetically engineered to overcome death signaling enhance adoptive cancer immunotherapy
Yamamoto, T. N., Lee, P.-H., Vodnala, S. K., Gurusamy, D., Kishton, R. J., Yu, Z., Eidizadeh, A., Eil, R., Fioravanti, J., Gattinoni, L., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci121491 · Cited by 156 · see citing works
Surviving apoptosis: life–death signaling in single cells
Flusberg, D. A., & Sorger, P. K. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.03.003 · Cited by 149 · see citing works
Cytokine and Chemokine Signals of T‐Cell Exclusion in Tumors
Zhang, Y., Guan, X.-Y., & Jiang, P. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.594609 · Cited by 133 · see citing works
Corsini, N. S., Sancho-Martinez, I., Laudenklos, S., Glagow, D., Kumar, S., Letellier, E., Koch, P., Teodorczyk, M., Kleber, S., Klussmann, S., et al. (2009) · Cell Stem Cell · doi:10.1016/j.stem.2009.05.004 · Cited by 129 · see citing works
Self-citationKallenberger, S. M., Beaudouin, J., Claus, J., Fischer, C., Sorger, P. K., Legewie, S., & Eils, R. (2014) · Science Signaling · doi:10.1126/scisignal.2004738 · Cited by 76 · see citing works
Death receptor Fas (CD95) signaling in the central nervous system: tuning neuroplasticity?
Reich, A., Spering, C., & Schulz, J. B. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.06.007 · Cited by 46 · see citing works
Wisniewski, P., Ellert-Miklaszewska, A., Kwiatkowska, A., & Kaminska, B. (2010) · Cellular Signalling · doi:10.1016/j.cellsig.2009.09.016 · Cited by 46 · see citing works
Infiltration of circulating myeloid cells through CD95L contributes to neurodegeneration in mice
Gao, L., Brenner, D., Llorens-Bobadilla, E., Saiz-Castro, G., Frank, T., Wieghofer, P., Hill, O., Thiemann, M., Karray, S., Prinz, M., et al. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20132423 · Cited by 42 · see citing works
Self-citationLigand stimulation of CD95 induces activation of Plk3 followed by phosphorylation of caspase-8
Helmke, C., Raab, M., Rödel, F., Matthess, Y., Oellerich, T., Mandal, R., Sanhaji, M., Urlaub, H., Rödel, C., Becker, S., et al. (2016) · Cell Research · doi:10.1038/cr.2016.78 · Cited by 44 · see citing works
- Authors
- Kleber, S., Sancho-Martinez, I., Wiestler, B., Beisel, A., Gieffers, C., Hill, O., Thiemann, M., Mueller, W., Sykora, J., Kuhn, A., Schreglmann, N., Letellier, E., Zuliani, C., Klussmann, S., Teodorczyk, M., Gröne, H.-J., Ganten, T. M., Sültmann, H., Tüttenberg, J., von Deimling, A., Regnier-Vigouroux, A., Herold-Mende, C., & Martin-Villalba, A.
- Affiliations
- German Cancer Research Center (DE)
- Apogenix (Germany) (DE)
- Heidelberg University (DE)
- University of Mannheim (DE)
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2008-03
- Volume
- 13
- Issue
- 3
- Pages
- 235-248
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2119928565
- Cited by
- 309
- References
- 2
- Citations by year
- 2026: 8 · 2025: 4 · 2024: 4 · 2023: 10 · 2022: 16 · 2021: 16 · 2020: 8 · 2019: 22 · 2018: 24 · 2017: 21 · 2016: 19 · 2015: 23 · 2014: 23 · 2013: 17 · 2012: 19
- FWCI
- 11.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1964 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Open Repository and Bibliography (University of Luxembourg) (submittedVersion, cc-by-nc-sa)
- Funders
- Bundesministerium für Bildung und Forschung
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- glioblastoma, tumor invasion, Fas, Fas ligand, Yes kinase, PI3K p85, Src family kinases, glycogen synthase kinase-3β, matrix metalloproteinases, intracranial tumor model
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Animals, Brain Neoplasms, Cell Movement, Glioblastoma, Humans, Neoplasm Invasiveness, Neoplasm Transplantation, Recombinant Fusion Proteins, Transfection, Transplantation, Isogeneic, Tumor Cells, Cultured, Signal Transduction, Apoptosis, fas Receptor, src-Family Kinases, Phosphatidylinositol 3-Kinases, Matrix Metalloproteinases, RNA Interference, RNA, Small Interfering, Glycogen Synthase Kinase 3, Cell Line, Tumor, Mice, Proto-Oncogene Proteins c-yes, Fas Ligand Protein, Death Domain Receptor Signaling Adaptor Proteins
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
