title: A truncated splice variant of human lysyl oxidase-like 2 promotes migration and invasion in esophageal squamous cell carcinoma.
abstract: Lysyl oxidase-like 2 (LOXL2) is a member of the lysyl oxidase family, which plays an important role in extracellular matrix protein biosynthesis and tumor progression. In the present study, we identified a novel splice variant, LOXL2Δ72, which encodes a peptide having the same N- and C-termini as wild-type LOXL2 (LOXL2WT), but lacks 72 nucleotides encoding 24 amino acids. LOXL2Δ72 had dramatically reduced enzymatic activity, and was no longer secreted. However, LOXL2Δ72 promoted greater cell migration and invasion than LOXL2WT. Furthermore, a dual luciferase reporter assay indicated that LOXL2Δ72 activates distinct signal transduction pathways compared to LOXL2WT, consistent with cDNA microarray data showing different expression levels of cell migration- and invasion-related genes induced following over-expression of each LOXL2 isoform. In particular, LOXL2Δ72 distinctly promoted esophageal squamous cell carcinoma (ESCC) cell migration via up-regulating the C-C motif chemokine ligand 28 (CCL28). Our results suggest that the new LOXL2 splice variant contributes to tumor progression by novel molecular mechanisms different from LOXL2WT.
authors.affiliation: Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Medical College of Shantou University, Shantou 515041, PR China; Department of Biochemistry and Molecular Biology, Medical College of Shantou University, Shantou 515041, PR China.
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Zou
authors.affiliation: Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Medical College of Shantou University, Shantou 515041, PR China; Department of Biochemistry and Molecular Biology, Medical College of Shantou University, Shantou 515041, PR China.
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Lv
authors.affiliation: Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Medical College of Shantou University, Shantou 515041, PR China; Department of Biochemistry and Molecular Biology, Medical College of Shantou University, Shantou 515041, PR China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Dai
authors.affiliation: Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Medical College of Shantou University, Shantou 515041, PR China; Department of Biochemistry and Molecular Biology, Medical College of Shantou University, Shantou 515041, PR China.
authors.forename: Xiu-Hui
authors.initials: XH
authors.lastname: Zhan
authors.affiliation: Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Medical College of Shantou University, Shantou 515041, PR China; Department of Biochemistry and Molecular Biology, Medical College of Shantou University, Shantou 515041, PR China.
authors.forename: Ji-Wei
authors.initials: JW
authors.lastname: Jiao
authors.affiliation: Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Medical College of Shantou University, Shantou 515041, PR China; Institute of Oncologic Pathology, Medical College of Shantou University, Shantou 515041, PR China.
authors.forename: Lian-Di
authors.initials: LD
authors.lastname: Liao
authors.affiliation: Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Medical College of Shantou University, Shantou 515041, PR China; Department of Laboratory Medicine, Huaihua Medical College, Huaihua 418000, PR China.
authors.forename: Tai-Mei
authors.initials: TM
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Medical College of Shantou University, Shantou 515041, PR China.
authors.forename: Chun-Quan
authors.initials: CQ
authors.lastname: Li
authors.affiliation: Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Medical College of Shantou University, Shantou 515041, PR China; Department of Biochemistry and Molecular Biology, Medical College of Shantou University, Shantou 515041, PR China.
authors.forename: Bing-Li
authors.initials: BL
authors.lastname: Wu
authors.affiliation: Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Medical College of Shantou University, Shantou 515041, PR China; Institute of Oncologic Pathology, Medical College of Shantou University, Shantou 515041, PR China. Electronic address: lyxu@stu.edu.cn.
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Xu
authors.affiliation: Key Laboratory of Molecular Biology in High Cancer Incidence Coastal Chaoshan Area of Guangdong Higher Education Institutes, Medical College of Shantou University, Shantou 515041, PR China; Department of Biochemistry and Molecular Biology, Medical College of Shantou University, Shantou 515041, PR China. Electronic address: nmli@stu.edu.cn.
authors.forename: En-Min
authors.initials: EM
authors.lastname: Li
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D003593:Cytoplasm / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D009361:Neoplasm Invasiveness; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D017384:Sequence Deletion
chemical_list: D020033:Protein Isoforms; D000594:Amino Acid Oxidoreductases; C119091:LOXL2 protein, human
keywords: Cell invasion; Cell migration; Lysyl oxidase activity; Lysyl oxidase-like 2; Splice variant