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. 2011 Jan;6(1):2-5.
doi: 10.1097/JTO.0b013e3181fd6b04.

GPC5 gene and its related pathways in lung cancer

Yafei Li  1 , Ping Yang
Affiliations

GPC5 gene and its related pathways in lung cancer

Yafei Li et al. J Thorac Oncol. 2011 Jan.

Erratum in

  • J Thorac Oncol. 2011 Apr;6(4):822
No abstract available

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Figures

Figure 1
Figure 1. Possible signal network of GPC5 in lung cancer development
The main function of membrane-attached GPC5 is thought to regulate the pathway signaling of Wnt, Hedgehogs (Hh), and fibroblast growth factors (FGFs). Depending on the biological context, GPC5 can either stimulate or inhibit cell signaling activity. GPC5 may bind to Wnt and to the Frizzled receptor in association with the co-receptors LRP5/6. Activation of the Frizzled receptor results in subsequent activation of Dishevelled. Through an unknown mechanism, Dishevelled inhibits the function of a multi-protein complex including Axin, APC, CK-γ, and GSK-β, which blocks phosphorylation of β-catenin and prevents its degradation. Increasing levels of free β-catenin translocate to the nucleus, complex with the TCF/LEF cofactors and activate target genes. In the case of the Hh pathway, it is proposed that GPC5 may inhibit the signaling by competing with Patched (the Hh receptor) for Hh binding. Binding Hh with the Patched receptor alters the interaction of Patched with Smoothened, a G protein-coupled receptor, resulting in the activation of Smoothened. This initiates a cascade of events resulting in the Gli entering the nucleus and acting as transcriptional activators. When the Hh signaling is lacking, Gli is bound to a multiprotein complex consisting of Fused (Fu) and the suppressor of Fu (SuFu) and will not enter the nucleus. GPC5 may activate the FGF pathway through unknown mechanisms. Following FGF ligand binding and receptor dimerization, the kinase domains transphosphorylate each other, leading to the docking of adaptor proteins and the activation of four key downstream pathways: RAS–RAF–MAPK, PI3K–AKT, signal transducer and activator of transcription (STAT) and phospholipase Cγ (PLCγ). The biological outcomes of FGF/FGFR activation are dependent on a complex network of signaling and transcriptional events regulated by multiple factors. CK-γ, casein kinase γ; GSK-β, glycogen synthase kinase β; APC, adenomatous polyposis coli; TCF, T cell–specific transcription factor; LEF, lymphoid enhancer–binding factor; Hh, hedgehog; Fu, fused; SuFu, suppressor of Fu; GPI, glycosylphosphatidylinositol; FGF, fibroblast growth factor; FGFR, fibroblast growth factor receptor; FRS2α, FGFR substrate 2α; GRB2, growth factor receptor-bound 2; Sos, son of sevenless; PLC γ, phospholipase C γ; STAT, signal-transducer and activator of transcription protein; MAPK, mitogen activated kinase-like protein.
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References

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