Entry
Name
Proteoglycans in cancer - Mus musculus (house mouse)
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: overview
BRITE hierarchy
Pathway map
Ortholog table
Organism
Mus musculus (house mouse) [GN:
mmu ]
Gene
15163 Hcls1; hematopoietic cell specific Lyn substrate 1 [KO:K06106 ]
14784 Grb2; growth factor receptor bound protein 2 [KO:K04364 ]
15461 Hras; Harvey rat sarcoma virus oncogene [KO:K02833 ]
16653 Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827 ]
20130 Rras; related RAS viral (r-ras) oncogene [KO:K07829 ]
66922 Rras2; related RAS viral (r-ras) oncogene 2 [KO:K07830 ]
29875 Iqgap1; IQ motif containing GTPase activating protein 1 [KO:K16848 ]
13712 Elk1; ELK1, member of ETS oncogene family [KO:K04375 ]
21844 Tiam1; T cell lymphoma invasion and metastasis 1 [KO:K05731 ]
16801 Arhgef1; Rho guanine nucleotide exchange factor (GEF) 1 [KO:K12330 ]
67653 4930544G11Rik; RIKEN cDNA 4930544G11 gene [KO:K04513 ]
14388 Gab1; growth factor receptor bound protein 2-associated protein 1 [KO:K09593 ]
18706 Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
18707 Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
74769 Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
18709 Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
18708 Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
18710 Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
20544 Slc9a1; solute carrier family 9 (sodium/hydrogen exchanger), member 1 [KO:K05742 ]
17931 Ppp1r12a; protein phosphatase 1, regulatory subunit 12A [KO:K06270 ]
329251 Ppp1r12b; protein phosphatase 1, regulatory subunit 12B [KO:K12329 ]
232807 Ppp1r12c; protein phosphatase 1, regulatory subunit 12C [KO:K17457 ]
69632 Arhgef12; Rho guanine nucleotide exchange factor (GEF) 12 [KO:K07532 ]
16438 Itpr1; inositol 1,4,5-trisphosphate receptor 1 [KO:K04958 ]
16439 Itpr2; inositol 1,4,5-triphosphate receptor 2 [KO:K04959 ]
16440 Itpr3; inositol 1,4,5-triphosphate receptor 3 [KO:K04960 ]
20848 Stat3; signal transducer and activator of transcription 3 [KO:K04692 ]
22160 Twist1; twist basic helix-loop-helix transcription factor 1 [KO:K09069 ]
13345 Twist2; twist basic helix-loop-helix transcription factor 2 [KO:K09069 ]
75705 Eif4b; eukaryotic translation initiation factor 4B [KO:K03258 ]
12575 Cdkn1a; cyclin-dependent kinase inhibitor 1A (P21) [KO:K06625 ]
21803 Tgfb1; transforming growth factor, beta 1 [KO:K13375 ]
12387 Ctnnb1; catenin (cadherin associated protein), beta 1 [KO:K02105 ]
15251 Hif1a; hypoxia inducible factor 1, alpha subunit [KO:K08268 ]
22339 Vegfa; vascular endothelial growth factor A [KO:K05448 ]
21859 Timp3; tissue inhibitor of metalloproteinase 3 [KO:K16866 ]
14103 Fasl; Fas ligand (TNF superfamily, member 6) [KO:K04389 ]
14102 Fas; Fas (TNF receptor superfamily member 6) [KO:K04390 ]
22059 Trp53; transformation related protein 53 [KO:K04451 ]
21808 Tgfb2; transforming growth factor, beta 2 [KO:K13376 ]
18793 Plaur; plasminogen activator, urokinase receptor [KO:K03985 ]
16412 Itgb1; integrin beta 1 (fibronectin receptor beta) [KO:K05719 ]
22408 Wnt1; wingless-type MMTV integration site family, member 1 [KO:K03209 ]
16402 Itga5; integrin alpha 5 (fibronectin receptor alpha) [KO:K06484 ]
327826 Frs2; fibroblast growth factor receptor substrate 2 [KO:K12461 ]
20662 Sos1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099 ]
20663 Sos2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099 ]
66911 Nudt16l1; nudix (nucleoside diphosphate linked moiety X)-type motif 16-like 1 [KO:K16867 ]
15200 Hbegf; heparin-binding EGF-like growth factor [KO:K08523 ]
22413 Wnt2; wingless-type MMTV integration site family, member 2 [KO:K00182 ]
22414 Wnt2b; wingless-type MMTV integration site family, member 2B [KO:K00182 ]
22415 Wnt3; wingless-type MMTV integration site family, member 3 [KO:K00312 ]
22416 Wnt3a; wingless-type MMTV integration site family, member 3A [KO:K00312 ]
22417 Wnt4; wingless-type MMTV integration site family, member 4 [KO:K00408 ]
22418 Wnt5a; wingless-type MMTV integration site family, member 5A [KO:K00444 ]
22419 Wnt5b; wingless-type MMTV integration site family, member 5B [KO:K00444 ]
22420 Wnt6; wingless-type MMTV integration site family, member 6 [KO:K00445 ]
22421 Wnt7a; wingless-type MMTV integration site family, member 7A [KO:K00572 ]
22422 Wnt7b; wingless-type MMTV integration site family, member 7B [KO:K00572 ]
20890 Wnt8a; wingless-type MMTV integration site family, member 8A [KO:K00714 ]
22423 Wnt8b; wingless-type MMTV integration site family, member 8B [KO:K00714 ]
216795 Wnt9a; wingless-type MMTV integration site family, member 9A [KO:K01064 ]
22412 Wnt9b; wingless-type MMTV integration site family, member 9B [KO:K01064 ]
22410 Wnt10b; wingless-type MMTV integration site family, member 10B [KO:K01357 ]
22409 Wnt10a; wingless-type MMTV integration site family, member 10A [KO:K01357 ]
22411 Wnt11; wingless-type MMTV integration site family, member 11 [KO:K01384 ]
93735 Wnt16; wingless-type MMTV integration site family, member 16 [KO:K01558 ]
15530 Hspg2; perlecan (heparan sulfate proteoglycan 2) [KO:K06255 ]
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 pathway
mmu04810 Regulation of actin cytoskeleton
KO pathway
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