title: ENO1, a potential prognostic head and neck cancer marker, promotes transformation partly via chemokine CCL20 induction.
abstract: The success of using glycolytic inhibitors for cancer treatment depends on studying the individual role of frequently deregulated glycolytic genes in cancer. This report aims to study the prognostic implication, and determine the cellular role and action mechanism of glycolytic ENO1 overexpression in head and neck cancer. The relationship of ENO1 mRNA expression in 44-pair clinical specimens with patient clinicopathologic characteristics was analysed by semi-quantitative RT-PCR, Kaplan-Meier survival curve and Cox model analyses. Following ectopic ENO1 expression or knockdown, we studied the proliferative, migratory, invasive, colony-forming and tumourigenic abilities of ENO1-genetically altered cells. DNA microarray analysis was used to identify downstream targets responsible for the ENO1 action in the cells. The expression of ENO1 mRNA was increased in 68% of tumour (T) specimens when compared to their normal (N) counterparts, and positively associated with clinical progression (p<0.05). High ENO1 expression (T/N2) was frequently observed in the patients with large primary tumours, late clinical stages or advanced neck metastasis. Moreover, high ENO1 patients had significantly poorer clinical outcomes than low expressers (T/N<2). Ectopic ENO1 expression stimulated cell transformation, invasion and tongue tumour formation. ENO1 knockdown abrogated the stimulation. Suppression of ENO1-induced proinflammatory CCL20 chemokine expression significantly attenuated its stimulatory effects on cell transformation and invasion. A concordant expression of ENO1 and CCL20 was validated both in ENO1-expressing cells and in clinical specimens. Together, we demonstrate a prognostic role of ENO1 overexpression in head and neck cancer and ENO1-mediated promotion of cell transformation and invasion partly via induced CCL20 expression.
authors.affiliation: Department of Otolaryngology, National Cheng Kung University Hospital, Tainan 70428, Taiwan, ROC.
authors.forename: Sen-Tien
authors.initials: ST
authors.lastname: Tsai
authors.forename: I-Hsiu
authors.initials: IH
authors.lastname: Chien
authors.forename: Wen-Hao
authors.initials: WH
authors.lastname: Shen
authors.forename: Yi-Zih
authors.initials: YZ
authors.lastname: Kuo
authors.forename: Ying-Tai
authors.initials: YT
authors.lastname: Jin
authors.forename: Tung-Yiu
authors.initials: TY
authors.lastname: Wong
authors.forename: Jenn-Ren
authors.initials: JR
authors.lastname: Hsiao
authors.forename: Hsing-Ping
authors.initials: HP
authors.lastname: Wang
authors.forename: Neng-Yao
authors.initials: NY
authors.lastname: Shih
authors.forename: Li-Wha
authors.initials: LW
authors.lastname: Wu
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D054418:Chemokine CCL20 / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D009361:Neoplasm Invasiveness; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014062:Tongue Neoplasms / Q000201:enzymology / Q000473:pathology; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D054418:Chemokine CCL20; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D025521:Tumor Suppressor Proteins; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase