alpha-enolase promotes tumorigenesis and metastasis via regulating AMPK/mTOR pathway in colorectal cancer.
alpha-enolase promotes tumorigenesis and metastasis via regulating AMPK/mTOR pathway in colorectal cancer.
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α-烯醇化酶通过调节 AMPK/mTOR 通路促进结直肠癌肿瘤发生和转移。
DOI：
10.1002/mc.22603
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发表时间：
2016
影响因子：
4.6
通讯作者：
Zhang Pengju
中科院分区：
文献类型：
--
作者：
Zhan Panpan;Zhao Shihu;Yan Hua;Yin Chunli;Xiao Yi;Wang Yunshan;Ni Ruoxuan;Chen Weiwen;Wei Guangwei;Zhang Pengju
α -烯醇化酶（ENO1）在多种类型的癌症中起关键作用，但其在结直肠癌（CRC）中的临床意义、功能作用和可能机制尚不清楚。采用qRT‐PCR、Western blot和免疫组织化学检测结直肠癌组织中ENO1的表达水平。通过MTT、集落形成、流式细胞术和体内致瘤能力分析研究ENO1对细胞生长的影响。ENO1对细胞迁移和侵袭的影响也通过划痕愈合、Transwell或Matrigel室试验和体内转移能力分析进行了探讨。结果显示，ENO1在结直肠癌组织中的表达水平显著升高。ENO1的高表达水平与结直肠癌患者的疾病进展相关。在HCT116细胞系中，ENO1的过表达促进了细胞在体外的增殖、迁移和侵袭以及体内的肿瘤发生和转移。另一方面，HCT116细胞中ENO1的消融导致完全相反的效果。在机制上，我们发现ENO1可以调节AMPK/mTOR信号通路。AMPK通路激活或mTOR通路抑制阻断了这些ENO1诱导的改变。总之，我们的研究结果表明，ENO1至少在一定程度上通过调节AMPK/mTOR通路，是CRC发生和转移的有效启动子。这些发现也提示ENO1可能是CRC患者一个有希望的治疗靶点。
The α‐enolase (ENO1) plays pivotal roles in several types of cancer, but its clinical significance, functional role, and possible mechanism in colorectal cancer (CRC) have remained unclear. Expression level of ENO1 in CRC tissues was examined by qRT‐PCR, Western blot, and immunohistochemistry. The effects of ENO1 on cell growth were investigated by MTT, colony formation, flow cytometry assays, andin vivotumorigenic capacity analysis. The impacts of ENO1 on cell migration and invasion were also explored by scratch‐healing, Transwell or Matrigel chamber assays, andin vivometastatic capacity analysis. Our results showed that the expression level of ENO1 was significantly elevated in CRC tissues. High expression level of ENO1 was associated with disease progression in CRC patients. Overexpression of ENO1 in HCT116 cell line promoted cell proliferation, migration, and invasionin vitroas well as tumorigenesis and metastasisin vivo. In other hand, ablation of ENO1 in HCT116 cells led to totally reverse effects. Mechanistically, we revealed ENO1 could regulate AMPK/mTOR signaling pathway. AMPK pathway activation or mTOR pathway suppression blocked these ENO1 induced alterations. Together, our results demonstrated that ENO1 is a potent promoter of CRC genesis and metastasis at least in part though regulating AMPK/mTOR pathway. These findings also suggested that ENO1 may be a promising therapeutic target in CRC patients.