title: Identification of a novel lysyl oxidase-like 2 alternative splicing isoform, LOXL2 Δe13, in esophageal squamous cell carcinoma.
abstract: Lysyl oxidase-like 2 (LOXL2) participates in every stage of cancer progression and promotes invasion and metastasis. In this study, we identified a novel alternative splicing isoform of LOXL2, namely LOXL2 Δe13, which lacked exon 13. Deletion of exon 13 caused an open reading frame shift and produced a truncated protein. LOXL2 Δe13 was expressed ubiquitously in cell lines and tissues and was mainly localized to the cytoplasm. Although it showed impaired deamination enzymatic activity compared with full-length LOXL2, LOXL2 Δe13 promoted the cell mobility and invasion of esophageal squamous cell carcinoma (ESCC) cells to greater degrees. In further research on the mechanisms, gene expression profiling and signaling pathway analysis revealed that LOXL2 Δe13 induced the expression of MAPK8 without affecting the FAK, AKT, and ERK signaling pathways. RNAi-mediated knockdown of MAPK8 could block the cell migration promoted by LOXL2De13, but it had little effect on that of full-length LOXL2. Our data suggest that LOXL2 Δe13 modulates the effects of cancer cell migration and invasion through a different mechanism from that of full-length LOXL2 and that it may play a very important role in tumor carcinogenesis and progression.
authors.affiliation: a The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China.
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Lv
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Zou
authors.forename: Lian-Di
authors.initials: LD
authors.lastname: Liao
authors.forename: Hui-Hui
authors.initials: HH
authors.lastname: Cao
authors.forename: Fa-Min
authors.initials: FM
authors.lastname: Zeng
authors.forename: Bing-Li
authors.initials: BL
authors.lastname: Wu
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Xie
authors.forename: Wang-Kai
authors.initials: WK
authors.lastname: Fang
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Xu
authors.forename: En-Min
authors.initials: EM
authors.lastname: Li
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000594:Amino Acid Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D004938:Esophageal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D009361:Neoplasm Invasiveness; D020033:Protein Isoforms / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology
chemical_list: D020033:Protein Isoforms; D000594:Amino Acid Oxidoreductases; C119091:LOXL2 protein, human; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human
keywords: ESCC; LOXL2; activité de désaminase; alternative splicing; deamination enzymatic activity; migration and invasion; migration et invasion; épissage alternatif