EYA4 functions as tumor suppressor gene and prognostic marker in pancreatic ductal adenocarcinoma through β-catenin/ID2 pathway

作者：Mo, Shi-Jing; Liu, Xin; Hao, Xiao-Yi; Chen, Wei; Zhang, Kun-Song; Cai, Jian-Peng; Lai, Jia-Ming; Liang, Li-Jian; Yin, Xiao-Yu^*

来源：Cancer Letters, 2016, 380(2): 403-412.

DOI：10.1016/j.canlet.2016.06.021

• EYA4
• beta-catenin/ID2 pathway
• Pancreatic ductal adenocarcinoma
• Tumor suppresser gene
• Prognostic marker

Eye absent homolog 4 (EYA4) was initially found as key gene in controlling eye development in Drosophila. We recently found that EYA4 was an independent prognostic factor in hepatocellular carcinoma. Its biological functions in malignancies remained unknown. The present study aimed at investigating its biological functions, molecular mechanisms and prognostic values in pancreatic ductal adenocarcinoma (PDAC). Overexpression of EYA4 in PDAC cells inhibited proliferation and invasion in vitro and tumor growth in vivo. Depletion of EYA4 in PDAC cells enhanced proliferation and invasion in vitro and tumor growth in vivo. Mechanistically, armed with the serine/threonine-specific protein phosphatase activity, EYA4 dephosphorylated beta-catenin at Ser675, blocked beta-catenin nuclear translocation and inhibited ID2 transactivation. Consistently, EYA4 expression inversely correlated with the levels of p-Ser675-beta catenin and ID2 in tissues. EYA4 expression in PDAC tissues was significantly reduced as compared with adjacent non-tumoral tissues. EYA4 expression was an independent prognostic factor in PDAC, with a lower EYA4 level in association with shorter long-term survival and disease-free time. We showed that EYA4 functioned as tumor suppressor gene in PDAC via repressing beta-catenin/ID2 activation, and was an independent prognostic factor in PDAC.

• 出版日期2016-10-1
• 单位中山大学