Entry Name Proteoglycans in cancer - Balaenoptera acutorostrata scammoni (minke whale)
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 Organism Balaenoptera acutorostrata scammoni (minke whale) [GN:
bacu ]
Gene 103007995 RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392 ]
103019637 IQGAP1; IQ motif containing GTPase activating protein 1 [KO:K16848 ]
103008077 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
103009307 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
103007464 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
103020020 PPP1R12A; protein phosphatase 1 regulatory subunit 12A [KO:K06270 ]
103012518 PPP1R12B; protein phosphatase 1 regulatory subunit 12B [KO:K12329 ]
103010788 PPP1R12C; protein phosphatase 1 regulatory subunit 12C [KO:K17457 ]
102997405 signal transducer and activator of transcription 3-like [KO:K04692 ]
103008157 STAT3; signal transducer and activator of transcription 3 (acute-phase response factor) [KO:K04692 ]
103016933 MYC; v-myc avian myelocytomatosis viral oncogene homolog [KO:K04377 ]
102999196 SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099 ]
103019365 SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099 ]
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 KO pathway LinkDB All DBs
