Entry Name Proteoglycans in cancer
Description Many proteoglycans (PGs) in the tumor microenvironment have been shown to be key macromolecules that contribute to biology of various types of cancer including proliferation, adhesion, angiogenesis and metastasis, affecting tumor progress. The four main types of proteoglycans include hyaluronan (HA), which does not occur as a PG but in free form, heparan sulfate proteoglycans (HSPGs), chondroitin sulfate proteoglycans (CSPGs), dematan sulfate proteoglycans (DSPG) and keratan sulfate proteoglycans (KSPGs) [BR:
00535 ]. Among these proteoglycans such as HA, acting with CD44, promotes tumor cell growth and migration, whereas other proteoglycans such as syndecans (-1~-4), glypican (-1, -3) and perlecan may interact with growth factors, cytokines, morphogens and enzymes through HS chains [BR:
00536 ], also leading to tumor growth and invasion. In contrast, some of the small leucine-rich proteolgycans, such as decorin and lumican, can function as tumor repressors, and modulate the signaling pathways by the interaction of their core proteins and multiple receptors.
Class Human Diseases; Cancer: overviewBRITE hierarchy
Pathway map Ortholog table Orthology K04364 growth factor receptor-bound protein 2
K05730 guanine nucleotide exchange factor VAV
K07829 Ras-related protein R-Ras
K07830 Ras-related protein R-Ras2
K07831 Ras-related protein M-Ras
K04365 B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04366 RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K08845 A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04392 Ras-related C3 botulinum toxin substrate 1
K16848 Ras GTPase-activating-like protein IQGAP1
K04393 cell division control protein 42
K04375 ETS domain-containing protein Elk-1
K08550 estrogen receptor alpha
K04503 G1/S-specific cyclin-D1
K05731 T-lymphoma invasion and metastasis-inducing protein 1
K12330 Rho guanine nucleotide exchange factor 1
K04513 Ras homolog gene family, member A
K09593 GRB2-associated-binding protein 1
K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K02649 phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K05742 solute carrier family 9 (sodium/hydrogen exchanger), member 1
K06269 serine/threonine-protein phosphatase PP1 catalytic subunit [EC:3.1.3.16 ]
K06270 protein phosphatase 1 regulatory subunit 12A
K12329 protein phosphatase 1 regulatory subunit 12B
K17457 protein phosphatase 1 regulatory subunit 12C
K07532 Rho guanine nucleotide exchange factor 12
K04958 inositol 1,4,5-triphosphate receptor type 1
K04959 inositol 1,4,5-triphosphate receptor type 2
K04960 inositol 1,4,5-triphosphate receptor type 3
K04515 calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17 ]
K04692 signal transducer and activator of transcription 3
K09295 homrobox protein Hox-D10
K05459 insulin-like growth factor 1
K03258 translation initiation factor 4B
K02991 small subunit ribosomal protein S6e
K06625 cyclin-dependent kinase inhibitor 1A
K13375 transforming growth factor beta-1
K16865 programmed cell death protein 4
K03156 tumor necrosis factor superfamily, member 2
K04377 Myc proto-oncogene protein
K08268 hypoxia-inducible factor 1 alpha
K09108 transcription factor AP-4
K05448 vascular endothelial growth factor A
K16866 metalloproteinase inhibitor 3
K04389 tumor necrosis factor ligand superfamily member 6
K04390 tumor necrosis factor receptor superfamily member 6
K13376 transforming growth factor beta-2
K04500 mothers against decapentaplegic homolog 2
K07965 heparanase 2 [EC:3.2.1.-]
K03985 plasminogen activator, urokinase receptor
K05460 hepatocyte growth factor
K03209 wingless-type MMTV integration site family, member 1
K18497 fibroblast growth factor 2
K12461 fibroblast growth factor receptor substrate 2
K07293 tyrosine-protein phosphatase non-receptor type 11 [EC:3.1.3.48 ]
K08523 heparin-binding EGF-like growth factor
K13769 insulin-like growth factor 2
K00182 wingless-type MMTV integration site family, member 2
K00312 wingless-type MMTV integration site family, member 3
K00408 wingless-type MMTV integration site family, member 4
K00444 wingless-type MMTV integration site family, member 5
K00445 wingless-type MMTV integration site family, member 6
K00572 wingless-type MMTV integration site family, member 7
K00714 wingless-type MMTV integration site family, member 8
K01064 wingless-type MMTV integration site family, member 9
K01357 wingless-type MMTV integration site family, member 10
K01384 wingless-type MMTV integration site family, member 11
K01558 wingless-type MMTV integration site family, member 16
K06255 basement membrane-specific heparan sulfate proteoglycan core protein
K09543 heat shock protein beta-2
Compound G13063 Binding domain for FGF2 in heparin/heparan sulfate
G13064 Binding domain for HGF in heparin/heparan sulfate
Reference Authors Bourguignon LY
Title Hyaluronan-mediated CD44 activation of RhoGTPase signaling and cytoskeleton function promotes tumor progression.
Journal Reference Authors Briggs MW, Sacks DB
Title IQGAP1 as signal integrator: Ca2+, calmodulin, Cdc42 and the cytoskeleton.
Journal Reference Authors Bourguignon LY, Singleton PA, Zhu H, Diedrich F
Title Hyaluronan-mediated CD44 interaction with RhoGEF and Rho kinase promotes Grb2-associated binder-1 phosphorylation and phosphatidylinositol 3-kinase signaling leading to cytokine (macrophage-colony stimulating factor) production and breast tumor progression.
Journal Reference Authors Bourguignon LY, Gilad E, Rothman K, Peyrollier K
Title Hyaluronan-CD44 interaction with IQGAP1 promotes Cdc42 and ERK signaling, leading to actin binding, Elk-1/estrogen receptor transcriptional activation, and ovarian cancer progression.
Journal Reference Authors Turley EA, Noble PW, Bourguignon LY
Title Signaling properties of hyaluronan receptors.
Journal Reference Authors Bourguignon LY, Zhu H, Chu A, Iida N, Zhang L, Hung MC
Title Interaction between the adhesion receptor, CD44, and the oncogene product, p185HER2, promotes human ovarian tumor cell activation.
Journal Reference Authors Neill T, Schaefer L, Iozzo RV
Title Decorin: a guardian from the matrix.
Journal Reference Authors Neill T, Painter H, Buraschi S, Owens RT, Lisanti MP, Schaefer L, Iozzo RV
Title Decorin antagonizes the angiogenic network: concurrent inhibition of Met, hypoxia inducible factor 1alpha, vascular endothelial growth factor A, and induction of thrombospondin-1 and TIMP3.
Journal Reference Authors Goldoni S, Humphries A, Nystrom A, Sattar S, Owens RT, McQuillan DJ, Ireton K, Iozzo RV
Title Decorin is a novel antagonistic ligand of the Met receptor.
Journal Reference Authors Zhu JX, Goldoni S, Bix G, Owens RT, McQuillan DJ, Reed CC, Iozzo RV
Title Decorin evokes protracted internalization and degradation of the epidermal growth factor receptor via caveolar endocytosis.
Journal Reference Authors Buraschi S, Pal N, Tyler-Rubinstein N, Owens RT, Neill T, Iozzo RV
Title Decorin antagonizes Met receptor activity and down-regulates {beta}-catenin and Myc levels.
Journal Reference Authors Goldoni S, Iozzo RV
Title Tumor microenvironment: Modulation by decorin and related molecules harboring leucine-rich tandem motifs.
Journal Reference Authors Sofeu Feugaing DD, Gotte M, Viola M
Title More than matrix: the multifaceted role of decorin in cancer.
Journal Reference Authors Merline R, Moreth K, Beckmann J, Nastase MV, Zeng-Brouwers J, Tralhao JG, Lemarchand P, Pfeilschifter J, Schaefer RM, Iozzo RV, Schaefer L
Title Signaling by the matrix proteoglycan decorin controls inflammation and cancer through PDCD4 and MicroRNA-21.
Journal Reference Authors Teng YH, Aquino RS, Park PW
Title Molecular functions of syndecan-1 in disease.
Journal Reference Authors Derksen PW, Keehnen RM, Evers LM, van Oers MH, Spaargaren M, Pals ST
Title Cell surface proteoglycan syndecan-1 mediates hepatocyte growth factor binding and promotes Met signaling in multiple myeloma.
Journal Reference Authors Fux L, Ilan N, Sanderson RD, Vlodavsky I
Title Heparanase: busy at the cell surface.
Journal Reference Authors Purushothaman A, Chen L, Yang Y, Sanderson RD
Title Heparanase stimulation of protease expression implicates it as a master regulator of the aggressive tumor phenotype in myeloma.
Journal Reference Authors Beauvais DM, Ell BJ, McWhorter AR, Rapraeger AC
Title Syndecan-1 regulates alphavbeta3 and alphavbeta5 integrin activation during angiogenesis and is blocked by synstatin, a novel peptide inhibitor.
Journal Reference Authors Mahtouk K, Tjin EP, Spaargaren M, Pals ST
Title The HGF/MET pathway as target for the treatment of multiple myeloma and B-cell lymphomas.
Journal Reference Authors Munesue S, Kusano Y, Oguri K, Itano N, Yoshitomi Y, Nakanishi H, Yamashina I, Okayama M
Title The role of syndecan-2 in regulation of actin-cytoskeletal organization of Lewis lung carcinoma-derived metastatic clones.
Journal Reference Authors Nugent MA, Iozzo RV
Title Fibroblast growth factor-2.
Journal Reference Authors Baciu PC, Saoncella S, Lee SH, Denhez F, Leuthardt D, Goetinck PF
Title Syndesmos, a protein that interacts with the cytoplasmic domain of syndecan-4, mediates cell spreading and actin cytoskeletal organization.
Journal J Cell Sci 113 Pt 2:315-24 (2000)
Reference Authors Thodeti CK, Albrechtsen R, Grauslund M, Asmar M, Larsson C, Takada Y, Mercurio AM, Couchman JR, Wewer UM
Title ADAM12/syndecan-4 signaling promotes beta 1 integrin-dependent cell spreading through protein kinase Calpha and RhoA.
Journal Reference Authors Beauvais DM, Rapraeger AC
Title Syndecans in tumor cell adhesion and signaling.
Journal Reference Authors Morgan MR, Humphries MJ, Bass MD
Title Synergistic control of cell adhesion by integrins and syndecans.
Journal Reference Authors Filmus J, Capurro M, Rast J
Title Glypicans.
Journal Reference Authors Filmus J, Capurro M
Title Glypican-3: a marker and a therapeutic target in hepatocellular carcinoma.
Journal Reference Authors Gao W, Ho M
Title The role of glypican-3 in regulating Wnt in hepatocellular carcinomas.
Journal Cancer Rep 1:14-19 (2011)
Reference Authors Filmus J, Capurro M
Title The role of glypicans in Hedgehog signaling.
Journal Reference Authors Cheng W, Tseng CJ, Lin TT, Cheng I, Pan HW, Hsu HC, Lee YM
Title Glypican-3-mediated oncogenesis involves the Insulin-like growth factor-signaling pathway.
Journal Reference Authors Iozzo RV, Sanderson RD
Title Proteoglycans in cancer biology, tumour microenvironment and angiogenesis.
Journal Reference Authors Nikitovic D, Katonis P, Tsatsakis A, Karamanos NK, Tzanakakis GN
Title Lumican, a small leucine-rich proteoglycan.
Journal Related ko04810 Regulation of actin cytoskeleton
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