title: Lysyl oxidase-like 4 (LOXL4) promotes proliferation and metastasis of gastric cancer via FAK/Src pathway.
abstract: BACKGROUND
  Lysyl oxidase-like 4 (LOXL4) has been found up-regulated in a variety of human malignancies, but its clinical significance and functional roles in gastric cancer (GC) remain unknown.
  
  
  METHODS
  Lysyl oxidase-like 4 (LOXL4) expression level in tumor tissues and human GC cell lines was evaluated by quantitative real-time polymerase chain reaction, Western blotting and immunohistochemical analyses. Its clinical significance was inferred from the analysis of 379 tissue samples of patients with GC using tissue microarray. The roles of LOXL4 in cell proliferation, migration and invasion in vitro were analyzed by gene over-expression, RNA interference and recombinant protein. Effects of LOXL4 on regulation of focal adhesion kinase/Src kinase (FAK/Src) pathway were examined by Western blotting.
  
  
  RESULTS
  Lysyl oxidase-like 4 (LOXL4) was up-regulated in GC tissues relative to paired non-tumor tissues, and this over-expression was significantly associated with tumor size, depth of tumor invasion, lymph node metastasis, tumor-node-metastasis (TNM) stages and poorer overall survival. Over-expression of LOXL4 has promotive effects on GC cell proliferation, migration and invasion in vitro, consistent with this, LOXL4 knockdown has inhibitive effects on GC cell proliferation, migration and invasion. Furthermore, recombinant human LOXL4 protein also promoted GC cell proliferation and migration. Subsequent mechanistic studies showed that LOXL4 could activate FAK/Src pathway to enhance cell-extracellular matrix adhesion.
  
  
  CONCLUSIONS
  Taken together, our data reveal that up-regulation of LOXL4 expression is a frequent event in GC progression, contributes to tumor cell proliferation and metastasis, and LOXL4 may be a potential independent prognostic marker and therapeutic target for GC.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 800 Dongchuan Road, Shanghai, 200240, China.
authors.forename: Rong-kun
authors.initials: RK
authors.lastname: Li
authors.forename: Wen-yi
authors.initials: WY
authors.lastname: Zhao
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.forename: Chun
authors.initials: C
authors.lastname: Zhuang
authors.forename: Xiao-xin
authors.initials: XX
authors.lastname: Zhang
authors.forename: Xiao-mei
authors.initials: XM
authors.lastname: Yang
authors.forename: Shu-heng
authors.initials: SH
authors.lastname: Jiang
authors.forename: Fan-zhi
authors.initials: FZ
authors.lastname: Kong
authors.forename: Lin
authors.initials: L
authors.lastname: Tu
authors.forename: Wen-ming
authors.initials: WM
authors.lastname: Zhang
authors.forename: Sheng-li
authors.initials: SL
authors.lastname: Yang
authors.forename: Hui
authors.initials: H
authors.lastname: Cao
authors.forename: Zhi-gang
authors.initials: ZG
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D000594:Amino Acid Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D008249:Protein-Lysine 6-Oxidase; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D000594:Amino Acid Oxidoreductases; C445682:LOXL4 protein, human; D008249:Protein-Lysine 6-Oxidase; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019061:src-Family Kinases