Pericyte FAK negatively regulates Gas6/Axl signalling to suppress tumour angiogenesis and tumour growth.

Animals Aorta, Thoracic / pathology Carcinoma, Lewis Lung / metabolism Cell Adhesion Cell Proliferation Cysteine-Rich Protein 61 / metabolism Female Focal Adhesion Kinase 1 / genetics Gene Expression Regulation, Neoplastic Humans Intercellular Signaling Peptides and Proteins / metabolism Lymphokines / metabolism Male Melanoma / blood supply Melanoma, Experimental Mice Mice, Inbred C57BL Mice, Knockout Neoplasms / pathology Neovascularization, Pathologic Pericytes / metabolism Placenta Growth Factor / metabolism Platelet-Derived Growth Factor / metabolism Proto-Oncogene Proteins / metabolism Proto-Oncogene Proteins c-sis / metabolism Receptor Protein-Tyrosine Kinases / metabolism Signal Transduction Tumor Microenvironment Vascular Endothelial Growth Factor A / metabolism Axl Receptor Tyrosine Kinase

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
04 06 2020
Historique:
received: 20 07 2018
accepted: 14 05 2020
entrez: 6 6 2020
pubmed: 6 6 2020
medline: 19 8 2020
Statut: epublish

Résumé

The overexpression of the protein tyrosine kinase, Focal adhesion kinase (FAK), in endothelial cells has implicated its requirement in angiogenesis and tumour growth, but how pericyte FAK regulates tumour angiogenesis is unknown. We show that pericyte FAK regulates tumour growth and angiogenesis in multiple mouse models of melanoma, lung carcinoma and pancreatic B-cell insulinoma and provide evidence that loss of pericyte FAK enhances Gas6-stimulated phosphorylation of the receptor tyrosine kinase, Axl with an upregulation of Cyr61, driving enhanced tumour growth. We further show that pericyte derived Cyr61 instructs tumour cells to elevate expression of the proangiogenic/protumourigenic transmembrane receptor Tissue Factor. Finally, in human melanoma we show that when 50% or more tumour blood vessels are pericyte-FAK negative, melanoma patients are stratified into those with increased tumour size, enhanced blood vessel density and metastasis. Overall our data uncover a previously unknown mechanism of tumour growth by pericytes that is controlled by pericyte FAK.

Identifiants

DOI: 10.1038/s41467-020-16618-6 PMID: 32499572 PMC: PMC7272651
pubmed: 32499572
doi: 10.1038/s41467-020-16618-6
pii: 10.1038/s41467-020-16618-6
pmc: PMC7272651
doi:

Substances chimiques

CCN1 protein, mouse 0
Cysteine-Rich Protein 61 0
Intercellular Signaling Peptides and Proteins 0
Lymphokines 0
PGF protein, human 0
Pdgfd protein, mouse 0
Pgf protein, mouse 0
Platelet-Derived Growth Factor 0
Proto-Oncogene Proteins 0
Proto-Oncogene Proteins c-sis 0
Vascular Endothelial Growth Factor A 0
growth arrest-specific protein 6 0
Placenta Growth Factor 144589-93-5
Receptor Protein-Tyrosine Kinases EC 2.7.10.1
Focal Adhesion Kinase 1 EC 2.7.10.2
Ptk2 protein, mouse EC 2.7.10.2
Axl Receptor Tyrosine Kinase 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2810

Subventions

Organisme : Worldwide Cancer Research
ID : 14-1328
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 24399
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C82181/A12007
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M019217/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 28990
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1000089
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 103749
Pays : United Kingdom

Commentaires et corrections

Type : ErratumIn

Références

Armulik, A., Genove, G. & Betsholtz, C. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev. Cell 21, 193–215 (2011).
pubmed: 21839917 doi: 10.1016/j.devcel.2011.07.001
Bergers, G. & Song, S. The role of pericytes in blood-vessel formation and maintenance. Neuro Oncol. 7, 452–464 (2005).
pubmed: 16212810 pmcid: 1871727 doi: 10.1215/S1152851705000232
Geevarghese, A. & Herman, I. M. Pericyte-endothelial crosstalk: implications and opportunities for advanced cellular therapies. Transl. Res. 163, 296–306 (2014).
pubmed: 24530608 pmcid: 3976718 doi: 10.1016/j.trsl.2014.01.011
Morikawa, S. et al. Abnormalities in pericytes on blood vessels and endothelial sprouts in tumors. Am. J. Pathol. 160, 985–1000 (2002).
pubmed: 11891196 pmcid: 1867175 doi: 10.1016/S0002-9440(10)64920-6
De Bock, K., Cauwenberghs, S. & Carmeliet, P. Vessel abnormalization: another hallmark of cancer? Molecular mechanisms and therapeutic implications. Curr. Opin. Genet. Dev. 21, 73–79 (2011).
pubmed: 21106363 doi: 10.1016/j.gde.2010.10.008
Rupp, C. et al. IGFBP7, a novel tumor stroma marker, with growth-promoting effects in colon cancer through a paracrine tumor-stroma interaction. Oncogene 34, 815–825 (2015).
pubmed: 24632618 doi: 10.1038/onc.2014.18
Luga, V. et al. Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell 151, 1542–1556 (2012).
pubmed: 23260141 doi: 10.1016/j.cell.2012.11.024
Caspani, E. M., Crossley, P. H., Redondo-Garcia, C. & Martinez, S. Glioblastoma: a pathogenic crosstalk between tumor cells and pericytes. PLoS ONE 9, e101402 (2014).
pubmed: 25032689 pmcid: 4102477 doi: 10.1371/journal.pone.0101402
Bose, A. et al. Tumor-derived vascular pericytes anergize Th cells. J. Immunol. 191, 971–981 (2013).
pubmed: 23785117 doi: 10.4049/jimmunol.1300280
Sulzmaier, F. J., Jean, C. & Schlaepfer, D. D. FAK in cancer: mechanistic findings and clinical applications. Nat. Rev. Cancer 14, 598–610 (2014).
pubmed: 25098269 pmcid: 4365862 doi: 10.1038/nrc3792
Lechertier, T. & Hodivala-Dilke, K. Focal adhesion kinase and tumour angiogenesis. J. Pathol. 226, 404–412 (2012).
pubmed: 21984450 doi: 10.1002/path.3018
Braren, R. et al. Endothelial FAK is essential for vascular network stability, cell survival, and lamellipodial formation. J. Cell Biol. 172, 151–162 (2006).
pubmed: 16391003 pmcid: 2063542 doi: 10.1083/jcb.200506184
Shen, T. L. et al. Conditional knockout of focal adhesion kinase in endothelial cells reveals its role in angiogenesis and vascular development in late embryogenesis. J. Cell Biol. 169, 941–952 (2005).
pubmed: 15967814 pmcid: 2171636 doi: 10.1083/jcb.200411155
Schlaepfer, D. D., Mitra, S. K. & Ilic, D. Control of motile and invasive cell phenotypes by focal adhesion kinase. Biochim. Biophys. Acta 1692, 77–102 (2004).
pubmed: 15246681 doi: 10.1016/j.bbamcr.2004.04.008
Lee, J., Borboa, A. K., Chun, H. B., Baird, A. & Eliceiri, B. P. Conditional deletion of the focal adhesion kinase FAK alters remodeling of the blood-brain barrier in glioma. Cancer Res. 70, 10131–10140 (2010).
pubmed: 21159635 pmcid: 3059220 doi: 10.1158/0008-5472.CAN-10-2740
Tavora, B. et al. Endothelial FAK is required for tumour angiogenesis. EMBO Mol. Med 2, 516–528 (2010).
pubmed: 21154724 pmcid: 3377344 doi: 10.1002/emmm.201000106
Hanahan, D. Heritable formation of pancreatic beta-cell tumours in transgenic mice expressing recombinant insulin/simian virus 40 oncogenes. Nature 315, 115–122 (1985).
pubmed: 2986015 doi: 10.1038/315115a0
Hellstrom, M. et al. Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. J. Cell Biol. 153, 543–553 (2001).
pubmed: 11331305 pmcid: 2190573 doi: 10.1083/jcb.153.3.543
Stratman, A. N. & Davis, G. E. Endothelial cell-pericyte interactions stimulate basement membrane matrix assembly: influence on vascular tube remodeling, maturation, and stabilization. Microsc. Microanal. 18, 68–80 (2012).
pubmed: 22166617 doi: 10.1017/S1431927611012402
Qian, B. Z. & Pollard, J. W. Macrophage diversity enhances tumor progression and metastasis. Cell 141, 39–51 (2010).
pubmed: 20371344 pmcid: 4994190 doi: 10.1016/j.cell.2010.03.014
Gustafsson, A., Bostrom, A. K., Ljungberg, B., Axelson, H. & Dahlback, B. Gas6 and the receptor tyrosine kinase Axl in clear cell renal cell carcinoma. PLoS ONE 4, e7575 (2009).
pubmed: 19888345 pmcid: 2766033 doi: 10.1371/journal.pone.0007575
Kanzaki, R. et al. Gas6 derived from cancer-associated fibroblasts promotes migration of Axl-expressing lung cancer cells during chemotherapy. Sci. Rep. 7, 10613 (2017).
pubmed: 28878389 pmcid: 5587707 doi: 10.1038/s41598-017-10873-2
Lemke, G. & Rothlin, C. V. Immunobiology of the TAM receptors. Nat. Rev. Immunol. 8, 327–336 (2008).
pubmed: 18421305 pmcid: 2856445 doi: 10.1038/nri2303
Collett, G. et al. Receptor tyrosine kinase Axl modulates the osteogenic differentiation of pericytes. Circ. Res. 92, 1123–1129 (2003).
pubmed: 12730092 doi: 10.1161/01.RES.0000074881.56564.46
Sieg, D. J. et al. Pyk2 and Src-family protein-tyrosine kinases compensate for the loss of FAK in fibronectin-stimulated signaling events but Pyk2 does not fully function to enhance FAK- cell migration. EMBO J. 17, 5933–5947 (1998).
pubmed: 9774338 pmcid: 1170921 doi: 10.1093/emboj/17.20.5933
Penzes, K. et al. Combined inhibition of AXL, Lyn and p130Cas kinases block migration of triple negative breast cancer cells. Cancer Biol. Ther. 15, 1571–1582 (2014).
pubmed: 25482942 pmcid: 4623058 doi: 10.4161/15384047.2014.956634
Jun, J. I. & Lau, L. F. Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets. Nat. Rev. Drug Discov. 10, 945–963 (2011).
pubmed: 22129992 pmcid: 3663145 doi: 10.1038/nrd3599
Leu, S. J., Lam, S. C. & Lau, L. F. Pro-angiogenic activities of CYR61 (CCN1) mediated through integrins alphavbeta3 and alpha6beta1 in human umbilical vein endothelial cells. J. Biol. Chem. 277, 46248–46255 (2002).
pubmed: 12364323 doi: 10.1074/jbc.M209288200
Fataccioli, V. et al. Stimulation of angiogenesis by Cyr61 gene: a new therapeutic candidate. Hum. Gene Ther. 13, 1461–1470 (2002).
pubmed: 12215267 doi: 10.1089/10430340260185094
D’Antonio, K. B. et al. Extracellular matrix associated protein CYR61 is linked to prostate cancer development. J. Urol. 183, 1604–1610 (2010).
pubmed: 20172544 pmcid: 3349619 doi: 10.1016/j.juro.2009.12.006
Schlegel, J. et al. MERTK receptor tyrosine kinase is a therapeutic target in melanoma. J. Clin. Invest. 123, 2257–2267 (2013).
pubmed: 23585477 pmcid: 3639697 doi: 10.1172/JCI67816
Axelrod, H. & Pienta, K. J. Axl as a mediator of cellular growth and survival. Oncotarget 5, 8818–8852 (2014).
pubmed: 25344858 pmcid: 4253401 doi: 10.18632/oncotarget.2422
Xie, D. et al. Breast cancer. Cyr61 is overexpressed, estrogen-inducible, and associated with more advanced disease. J. Biol. Chem. 276, 14187–14194 (2001).
pubmed: 11297518 doi: 10.1074/jbc.M009755200
Gery, S. et al. Ovarian carcinomas: CCN genes are aberrantly expressed and CCN1 promotes proliferation of these cells. Clin. Cancer Res. 11, 7243–7254 (2005).
pubmed: 16243794 doi: 10.1158/1078-0432.CCR-05-0231
Tsai, M. S., Hornby, A. E., Lakins, J. & Lupu, R. Expression and function of CYR61, an angiogenic factor, in breast cancer cell lines and tumor biopsies. Cancer Res. 60, 5603–5607 (2000).
pubmed: 11059746
Ruf, W., Yokota, N. & Schaffner, F. Tissue factor in cancer progression and angiogenesis. Thromb. Res. 125, S36–S38 (2010).
pubmed: 20434002 doi: 10.1016/S0049-3848(10)70010-4
Baker, E. A., Leaper, D. J., Hayter, J. P. & Dickenson, A. J. Plasminogen activator system in oral squamous cell carcinoma. Br. J. Oral Maxillofac. Surg. 45, 623–627 (2007).
pubmed: 17590247 doi: 10.1016/j.bjoms.2007.04.021
Dano, K. et al. Plasminogen activation and cancer. Thromb. Haemost. 93, 676–681 (2005).
pubmed: 15841311 doi: 10.1160/TH05-01-0054
Chen, X. L. et al. VEGF-induced vascular permeability is mediated by FAK. Dev. Cell 22, 146–157 (2012).
pubmed: 22264731 pmcid: 3266538 doi: 10.1016/j.devcel.2011.11.002
Jean, C. et al. Inhibition of endothelial FAK activity prevents tumor metastasis by enhancing barrier function. J. Cell Biol. 204, 247–263 (2014).
pubmed: 24446483 pmcid: 3897185 doi: 10.1083/jcb.201307067
Raza, A., Franklin, M. J. & Dudek, A. Z. Pericytes and vessel maturation during tumor angiogenesis and metastasis. Am. J. Hematol. 85, 593–598 (2010).
pubmed: 20540157 doi: 10.1002/ajh.21745
Song, X. et al. Overexpression of receptor tyrosine kinase Axl promotes tumor cell invasion and survival in pancreatic ductal adenocarcinoma. Cancer 117, 734–743 (2011).
pubmed: 20922806 doi: 10.1002/cncr.25483
van Ginkel, P. R. et al. Expression of the receptor tyrosine kinase Axl promotes ocular melanoma cell survival. Cancer Res. 64, 128–134 (2004).
pubmed: 14729616 doi: 10.1158/0008-5472.CAN-03-0245
Gothert, J. R. et al. Genetically tagging endothelial cells in vivo: bone marrow-derived cells do not contribute to tumor endothelium. Blood 104, 1769–1777 (2004).
pubmed: 15187022 doi: 10.1182/blood-2003-11-3952
Liu, H. et al. Cysteine-rich protein 61 and connective tissue growth factor induce deadhesion and anoikis of retinal pericytes. Endocrinology 149, 1666–1677 (2008).
pubmed: 18187544 doi: 10.1210/en.2007-1415
Sun, Z. J. et al. Involvement of Cyr61 in growth, migration, and metastasis of prostate cancer cells. Br. J. Cancer 99, 1656–1667 (2008).
pubmed: 18941464 pmcid: 2584944 doi: 10.1038/sj.bjc.6604712
Abe, K. et al. Regulation of vascular endothelial growth factor production and angiogenesis by the cytoplasmic tail of tissue factor. Proc. Natl Acad. Sci. USA 96, 8663–8668 (1999).
pubmed: 10411932 pmcid: 17573 doi: 10.1073/pnas.96.15.8663
Baker, M. et al. Use of the mouse aortic ring assay to study angiogenesis. Nat. Protoc. 7, 89–104 (2012).
doi: 10.1038/nprot.2011.435
Reynolds, L. E. & Hodivala-Dilke, K. M. Primary mouse endothelial cell culture for assays of angiogenesis. Methods Mol. Med. 120, 503–509 (2006).
pubmed: 16491622
Tigges, U., Welser-Alves, J. V., Boroujerdi, A. & Milner, R. A novel and simple method for culturing pericytes from mouse brain. Microvasc. Res. 84, 74–80 (2012).
pubmed: 22484453 pmcid: 3748138 doi: 10.1016/j.mvr.2012.03.008
Reynolds, L. E. et al. Dual role of pericyte alpha6beta1-integrin in tumour blood vessels. J. Cell Sci. 130, 1583–1595 (2017).
pubmed: 28289267 pmcid: 5450232

Auteurs

Tanguy Lechertier (T)

Centre for Tumour Biology, Barts Cancer Institute - a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, UK.

Louise E Reynolds (LE)

Centre for Tumour Biology, Barts Cancer Institute - a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, UK.
ORCID: 0000-0001-6075-1808

Hyojin Kim (H)

Cell Death & Inflammation, The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research, Fulham Road, London, SW3 6JB, UK.

Ana Rita Pedrosa (AR)

Centre for Tumour Biology, Barts Cancer Institute - a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, UK.

Jesús Gómez-Escudero (J)

Centre for Tumour Biology, Barts Cancer Institute - a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, UK.

José M Muñoz-Félix (JM)

Centre for Tumour Biology, Barts Cancer Institute - a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, UK.

Silvia Batista (S)

Systems Oncology Group, Champalimaud Research, Champalimaud Centre for the Unknown Av. Brasília, Doca de Pedrouços, 1400-038, Lisbon, Portugal.

Matthew Dukinfield (M)

Centre for Tumour Biology, Barts Cancer Institute - a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, UK.

Fevzi Demircioglu (F)

Centre for Tumour Biology, Barts Cancer Institute - a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, UK.

Ping Pui Wong (PP)

Centre for Tumour Biology, Barts Cancer Institute - a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, UK.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 510120, Guangzhou, China.

Kylie P Matchett (KP)

Centre for Inflammation Research, The Queen's Medical Research Institute, Edinburgh BioQuarter, University of Edinburgh, Edinburgh, UK.
ORCID: 0000-0001-8710-7721

Neil C Henderson (NC)

Centre for Inflammation Research, The Queen's Medical Research Institute, Edinburgh BioQuarter, University of Edinburgh, Edinburgh, UK.
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road South, Edinburgh, UK.
ORCID: 0000-0002-2273-4094

Gabriela D'Amico (G)

Centre for Tumour Biology, Barts Cancer Institute - a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, UK.

Maddy Parsons (M)

Nikon Imaging Centre@King's, Randall Division of Cell and Molecular Biophysics, Kings College London, Room 3.22B, New Hunts House Guys Campus, London, SE1 1UL, UK.
ORCID: 0000-0002-2021-8379

Catherine Harwood (C)

Centre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT, UK.

Pascal Meier (P)

Cell Death & Inflammation, The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research, Fulham Road, London, SW3 6JB, UK.

Kairbaan M Hodivala-Dilke (KM)

Centre for Tumour Biology, Barts Cancer Institute - a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, UK. k.hodivala-dilke@qmul.ac.uk.
ORCID: 0000-0002-2859-749X

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Système cardiovasculaire › Vaisseaux sanguins › Artères › Aorte › Aorte thoracique › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Tumeurs › Carcinome pulmonaire de Lewis › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Adhérence cellulaire › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines CCN de signalisation intercellulaire › Protéine-61 riche en cystéine › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Phosphoprotéines › Focal adhesion kinase 1 › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Lymphokines › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Naevus et mélanomes › Mélanome › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Techniques d'investigation › Modèles animaux › Tumeurs expérimentales › Mélanome expérimental › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Tumeurs › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Métaplasie › Néovascularisation pathologique › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Structures de l'embryon › Feuillets embryonnaires › Mésoderme › Péricytes › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de la grossesse › Facteur de croissance placentaire › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Facteur de croissance dérivé des plaquettes › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › Protéines proto-oncogènes › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Facteur de croissance dérivé des plaquettes › Protéines proto-oncogènes c-sis › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs à activité tyrosine kinase › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Microenvironnement tumoral › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines angiogéniques › Facteurs de croissance endothéliale vasculaire › Facteur de croissance endothéliale vasculaire de type A › Pericyte FAK negatively regulates Gas6/Axl...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › Protéines proto-oncogènes › Axl Receptor Tyrosine Kinase › Pericyte FAK negatively regulates Gas6/Axl...