KEGG   PATHWAY: map05205
Entry
map05205                    Pathway                                
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: overview
Pathway map
map05205  Proteoglycans in cancer
map05205

Reference
  Authors
Bourguignon LY
  Title
Hyaluronan-mediated CD44 activation of RhoGTPase signaling and cytoskeleton function promotes tumor progression.
  Journal
Semin Cancer Biol 18:251-9 (2008)
DOI:10.1016/j.semcancer.2008.03.007
Reference
  Authors
Briggs MW, Sacks DB
  Title
IQGAP1 as signal integrator: Ca2+, calmodulin, Cdc42 and the cytoskeleton.
  Journal
FEBS Lett 542:7-11 (2003)
DOI:10.1016/S0014-5793(03)00333-8
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
J Biol Chem 278:29420-34 (2003)
DOI:10.1074/jbc.M301885200
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
J Biol Chem 280:11961-72 (2005)
DOI:10.1074/jbc.M411985200
Reference
  Authors
Turley EA, Noble PW, Bourguignon LY
  Title
Signaling properties of hyaluronan receptors.
  Journal
J Biol Chem 277:4589-92 (2002)
DOI:10.1074/jbc.R100038200
Reference
PMID:9346940
  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
J Biol Chem 272:27913-8 (1997)
DOI:10.1074/jbc.272.44.27913
Reference
  Authors
Neill T, Schaefer L, Iozzo RV
  Title
Decorin: a guardian from the matrix.
  Journal
Am J Pathol 181:380-7 (2012)
DOI:10.1016/j.ajpath.2012.04.029
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
J Biol Chem 287:5492-506 (2012)
DOI:10.1074/jbc.M111.283499
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
J Cell Biol 185:743-54 (2009)
DOI:10.1083/jcb.200901129
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
J Biol Chem 280:32468-79 (2005)
DOI:10.1074/jbc.M503833200
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
J Biol Chem 285:42075-85 (2010)
DOI:10.1074/jbc.M110.172841
Reference
  Authors
Goldoni S, Iozzo RV
  Title
Tumor microenvironment: Modulation by decorin and related molecules harboring leucine-rich tandem motifs.
  Journal
Int J Cancer 123:2473-9 (2008)
DOI:10.1002/ijc.23930
Reference
  Authors
Sofeu Feugaing DD, Gotte M, Viola M
  Title
More than matrix: the multifaceted role of decorin in cancer.
  Journal
Eur J Cell Biol 92:1-11 (2013)
DOI:10.1016/j.ejcb.2012.08.004
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
Sci Signal 4:ra75 (2011)
DOI:10.1126/scisignal.2001868
Reference
  Authors
Teng YH, Aquino RS, Park PW
  Title
Molecular functions of syndecan-1 in disease.
  Journal
Matrix Biol 31:3-16 (2012)
DOI:10.1016/j.matbio.2011.10.001
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
Blood 99:1405-10 (2002)
DOI:10.1182/blood.V99.4.1405
Reference
  Authors
Fux L, Ilan N, Sanderson RD, Vlodavsky I
  Title
Heparanase: busy at the cell surface.
  Journal
Trends Biochem Sci 34:511-9 (2009)
DOI:10.1016/j.tibs.2009.06.005
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
J Biol Chem 283:32628-36 (2008)
DOI:10.1074/jbc.M806266200
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
J Exp Med 206:691-705 (2009)
DOI:10.1084/jem.20081278
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
Biochim Biophys Acta 1806:208-19 (2010)
DOI:10.1016/j.bbcan.2010.07.006
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
Biochem J 363:201-9 (2002)
DOI:10.1042/bj3630201
Reference
  Authors
Nugent MA, Iozzo RV
  Title
Fibroblast growth factor-2.
  Journal
Int J Biochem Cell Biol 32:115-20 (2000)
DOI:10.1016/S1357-2725(99)00123-5
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
J Biol Chem 278:9576-84 (2003)
DOI:10.1074/jbc.M208937200
Reference
  Authors
Beauvais DM, Rapraeger AC
  Title
Syndecans in tumor cell adhesion and signaling.
  Journal
Reprod Biol Endocrinol 2:3 (2004)
DOI:10.1186/1477-7827-2-3
Reference
  Authors
Morgan MR, Humphries MJ, Bass MD
  Title
Synergistic control of cell adhesion by integrins and syndecans.
  Journal
Nat Rev Mol Cell Biol 8:957-69 (2007)
DOI:10.1038/nrm2289
Reference
  Authors
Filmus J, Capurro M, Rast J
  Title
Glypicans.
  Journal
Genome Biol 9:224 (2008)
DOI:10.1186/gb-2008-9-5-224
Reference
  Authors
Filmus J, Capurro M
  Title
Glypican-3: a marker and a therapeutic target in hepatocellular carcinoma.
  Journal
FEBS J 280:2471-6 (2013)
DOI:10.1111/febs.12126
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
Matrix Biol 35:248-52 (2014)
DOI:10.1016/j.matbio.2013.12.007
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
Carcinogenesis 29:1319-26 (2008)
DOI:10.1093/carcin/bgn091
Reference
  Authors
Iozzo RV, Sanderson RD
  Title
Proteoglycans in cancer biology, tumour microenvironment and angiogenesis.
  Journal
J Cell Mol Med 15:1013-31 (2011)
DOI:10.1111/j.1582-4934.2010.01236.x
Reference
  Authors
Nikitovic D, Katonis P, Tsatsakis A, Karamanos NK, Tzanakakis GN
  Title
Lumican, a small leucine-rich proteoglycan.
  Journal
IUBMB Life 60:818-23 (2008)
DOI:10.1002/iub.131
Related
pathway
map04010  MAPK signaling pathway
map04020  Calcium signaling pathway
map04066  HIF-1 signaling pathway
map04150  mTOR signaling pathway
map04151  PI3K-Akt signaling pathway
map04210  Apoptosis
map04310  Wnt signaling pathway
map04340  Hedgehog signaling pathway
map04350  TGF-beta signaling pathway
map04370  VEGF signaling pathway
map04510  Focal adhesion
map04520  Adherens junction
map04810  Regulation of actin cytoskeleton
KO pathway
ko05205   
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