FIGURE 3 | PGE2 and LTB4 promote cancer progression through the induction of tumour epithelial cell proliferation, survival, and migration and invasion.

From the following article:

Eicosanoids and cancer

Dingzhi Wang & Raymond N. DuBois

Nature Reviews Cancer 10, 181-193 (March 2010)

doi:10.1038/nrc2809

Eicosanoids and cancer

Multiple cellular signalling pathways mediate the effects of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) on the regulation of epithelial tumour cell proliferation, survival, and migration and invasion. PGE2 stimulates cell proliferation through multiple cascades in both colorectal cancer (CRC) and non-small-cell lung cancer cells. PGE2 also induces cell proliferation through a glycogen synthase kinase-3β (GSK3β)–β-catenin (β-cat) pathway in CRC cells or by the upregulation of aromatase in breast cancer cells. PGE2 inhibition of GSK3β reduces β-catenin phosphorylation and thereby prevents its degradation, leading to accumulation, nuclear translocation and functional activity of β-catenin. PGE2 promotes CRC cell survival by activating a PI3K–Akt– peroxisome proliferator-activated receptor-δ (PPARδ) cascade in vitro and in vivo. In addition, PGE2 induces CRC cell migration and invasion through β-arrestin-1–SRC–epidermal growth factor receptor (EGFR)–PI3K–Akt signalling in vitro and in vivo. PGE2 transactivation of EGFR also depends on the extracellular release of an EGF-like ligand in CRC cell lines and a normal gastric epithelial cell line. PGE2 also induces cell migration and invasion through an Erk–ETS1–matrix metalloproteinase 2 (MMP2) cascade in pancreatic cancer cell lines or through the upregulation of C-C chemokine receptor 7 (CCR7) in breast cancer cell lines. LTB4 stimulates cell proliferation and promotes cell survival through a BLT1–Erk pathway in CRC cell lines or through both Mek–Erk and PI3K–Akt pathways in human pancreatic cancer cell lines. P, phosphorylation.

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