title: α-enolase promotes tumorigenesis and metastasis via regulating AMPK/mTOR pathway in colorectal cancer.
abstract: 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, and in vivo tumorigenic capacity analysis. The impacts of ENO1 on cell migration and invasion were also explored by scratch-healing, Transwell or Matrigel chamber assays, and in vivo metastatic 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 invasion in vitro as well as tumorigenesis and metastasis in 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, Shandong, P.R. China.|Chinese Academy of Medical Sciences and Peking Union Medical College, National Cancer Center/Cancer Hospital, Beijing, P.R. China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Zhan
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, Shandong, P.R. China.
authors.forename: Shihu
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Spleen and Stomach Diseases, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, Shandong, P.R. China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Yin
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, Shandong, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Anatomy and Key Laboratory of Experimental Teratology, Ministry of Education, Shandong University School of Medicine, Jinan, Shandong, P.R. China.
authors.forename: Yunshan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Anatomy and Key Laboratory of Experimental Teratology, Ministry of Education, Shandong University School of Medicine, Jinan, Shandong, P.R. China.
authors.forename: Ruoxuan
authors.initials: R
authors.lastname: Ni
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, Shandong, P.R. China.
authors.forename: Weiwen
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Anatomy and Key Laboratory of Experimental Teratology, Ministry of Education, Shandong University School of Medicine, Jinan, Shandong, P.R. China.
authors.forename: Guangwei
authors.initials: G
authors.lastname: Wei
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, Shandong, P.R. China.
authors.forename: Pengju
authors.initials: P
authors.lastname: Zhang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D006801:Humans; D008807:Mice, Inbred BALB C; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase
keywords: AMPK; ENO1; colorectal cancer; mTOR; tumorigenesis