Matricellular Proteins: A Sticky Affair with Cancers

Table 1

Overview of the marticellular protein cell-adhesion signaling pathways and their biological and clinical implications.

Matricellular protein	Cell adhesion partner(s)	Signaling pathways	Cellular and biological effects	Clinical implications
ANGPTL4	Vitronectin, Fibronectin, Integrin β1, β5	TGFβ via smad signaling, redox-based pro-survival via PI3K/PKB and ERK1/2 downstream survival pathways	Regulates ECM availability, cell migration, angiogenesis confers anoikis effect on tumor cells	Wound repair, cancer metastasis
Cyr61	Integrin α2β1, α6β1, αDβ2, αMβ2, αIIbβ3, αvβ3, αvβ5 Syndecan-4, perclean	PI3K/PKB, ERK1/2, MAPK, NF-κB signaling pathways	Promotes cell proliferation, motility, survival, invasiveness confers anti-apoptotic phentotype	Cancer metastasis and tumorigenesis
OPN	CD44, integrin αvβ1, αvβ3, and αvβ5	NF-κB,VEGF signaling, Src-mediated “inside-out” signaling, integrin-linked ILK, and PKB survival pathway	Integrin-mediated cancer cell migration, angiogenesis, inhibition of apoptosis ECM degradation via MMPs	Cancer metastasis
SPARC	Integrin α5β1	PKB prosurvival pathway		Cancer metastasis
TNC	Fibronectin, syndecan-4	MAPK, Wnt, TGFβ, EGFR, HGF, c-Met signaling pathways	Induction of TNC expression, cell proliferation, migration, invasion Downregulation of DKK-1, increased express and nuclear accumulation of β-catenin	Cancer metastasis
TSP1	Integrin α3β1, α4β1, α6β1, αvβ3 CD 47, CD36	Fyn, capase-3, and p38 MAPK, inhibit eNOS/NO signaling, inhibit VEGF/VEGFR2 signaling pathways	Inhibit endothelial cell migration to reduce angiogenesis, modulate level of sGC and cGMP-dependent protein kinase in endothelial cells	Inhibit metastasis via its antiangiogenic phenotype