NHERF1 regulates the progression of colorectal cancer through the interplay with VEGFR2 pathway.
NHERF1 regulates the progression of colorectal cancer through the interplay with VEGFR2 pathway.
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NHERF1通过与VEGFR2通路相互作用调节结直肠癌的进展
DOI：
10.18632/oncotarget.13949
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发表时间：
2017-01-31
期刊：
影响因子：
--
通讯作者：
Jiang WG
中科院分区：
文献类型：
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作者：
Gu Y;Yu H;Hao C;Martin TA;Hargest R;He J;Cheng S;Jiang WG
Na+/H+交换调节因子1（NHERF 1）的异位表达在结直肠癌中的致癌作用最近被提出，其中NHERF 1在肿瘤缺氧微环境中发挥作用。我们发现NHERF 1在结直肠癌组织中有高水平表达，并且NHERF 1的表达与VEGFR 2的表达呈正相关。结直肠癌中VEGFR 2表达的预后价值依赖于NHERF 1的表达。低氧诱导结肠癌细胞NHERF 1表达上调依赖于VEGFR 2信号的激活。NHERF 1反过来抑制VEGFR 2信号的激活，这可能是由NHERF 1和VEGFR 2之间的相互作用调节，导致结肠癌细胞的迁移和侵袭减少。这些结果表明NHERF 1和VEGFR 2信号在结直肠癌中的动态相互作用，这可以解释NHERF 1对调节肿瘤细胞对缺氧微环境的反应的贡献。
The oncogenic role of ectopic expression of Na+/H+ exchanger regulatory factor 1 (NHERF1) was recently suggested in colorectal cancer, where it was implicated in playing a role in the tumor hypoxia microenvironment. Here we showed that a high level expression of NHERF1 was found in colorectal cancer tissues and that the expression of NHERF1 was positively correlated with VEGFR2 expression. The prognostic value of VEGFR2 expression in colorectal cancer relied on the expression of NHERF1. The up-regulation of NHERF1 induced by the exposure to hypoxia in colon cancer cells depended on the activation of VEGFR2 signaling. NHERF1 in turn inhibited the activation of VEGFR2 signaling which could be regulated by the interaction between NHERF1 and VEGFR2, resulting in the reduction of migration and invasion of colon cancer cells. These results suggest a dynamic interplay between NHERF1 and VEGFR2 signaling in colorectal cancer, which could explain the contribution of NHERF1 to the regulation of tumor cell responses to the hypoxia microenvironment.