Fig. 6: CXCR7 accelerates HIF-1α translation by facilitating Src-mediated eIF4E phosphorylation.

a HIF-1α expression in murine melanoma cells treated with MG132 (10 μM). b The effects of CXCR7 modifications on eIF4E phosphorylation in melanoma cells. c, d CXCL12 stimulated eIF4E phosphorylation through the Src signaling in melanoma cells. F10 WT (c) and A375 WT (d) cells were starved overnight. After pretreated with AMD3100 (1 μg/ml) combined with PP1 (10 μM) or U0126 (10 μM) for 1 h, the cells were stimulated with recombinant murine (50 ng/ml) or human (100 ng/ml) CXCL12 as indicated. The cell lysates were collected and immunoblotted with the indicated antibodies. e A375 WT and KO cells were pretreated with cercosporamide (cerco, 20 μM) overnight and then incubated with CoCl₂ (200 μM) for 4 h. The levels of HIF-1α and phosphorylated eIF4E were examined by western blot. f The proposed model for the functions of CXCR7 in melanoma tumorigenesis. CXCR7 is activated by CXCL12 to support melanoma cell proliferation through β-arrestin2-mediated Src phosphorylation. In addition, the activation of this CXCR7-Src axis stimulates eIF4E phosphorylation to accelerate the translation of HIF-1α, which enhances the secretion of VEGF to facilitate melanoma angiogenesis