ANXA2 promotes esophageal cancer progression by activating MYC-HIF1A-VEGF axis

Abstract

Aberrantly expressed ANXA2 is observed in a wide range of malignancies, including ESCC, and plays pivotal roles in tumor formation and progression by modulating cell proliferation, apoptosis, adhesion, invasion, metastasis, and tumor neovascularization [4, 6–11]. [...]inhibition of ANXA2 can suppress tumor cell proliferation, survival and metastasis [4, 8, 12–15]. Notably, a cycloheximide chase assay showed that overexpression of ANXA2Y23D led to more stable ANXA2 protein compared with ANXA2Y23A overexpression (Fig. 5d). [...]treatment of cells with the proteasome inhibitor MG132 led to accumulation of ubiquitinated MYC protein in ANXA2Y23A- but not ANXA2Y23D-overexpressing ESCC cells (Fig. 5e). Herein, we demonstrate that highly expressed p-ANXA2 promotes the invasion and metastasis of ESCC cells through upregulation of MYC-HIF1A-VEGF cascade. [...]this study revealed that phosphorylation of ANXA2 at Tyr23 by SRC increases MYC protein abundance through inhibiting its proteasomal degradation in ESCC cells. Conclusions Our current findings demonstrate that ANXA2 plays critical roles in the ESCC progression by activating the MYC-HIF1A-VEGF signaling pathway. [...]these data suggest that inhibition of SRC-ANXA2-MYC-HIF1A-VEGF signaling may offer a potential therapeutic strategy for patients with ESCC.