title: Thioredoxin-like protein 2 is overexpressed in colon cancer and promotes cancer cell metastasis by interaction with ran.
abstract: OBJECTIVE
  Our previous work identified thioredoxin-like protein 2 (Txl-2) as the target of the monoclonal antibody MC3 associated with colon cancer, but its underlying mechanisms remain poorly understood. Txl-2, a novel thioredoxin (Trx) and nucleoside diphosphate kinase family member, is alternatively spliced and gives rise to three different Txl-2 isoforms. In this study, Txl-2 expression in colon cancer, differential functions for Txl-2 isoforms in cell invasion and metastasis, and the downstream signaling were investigated.
  
  
  RESULTS
  Txl-2 expression was elevated in colon cancer tissues compared to normal colonic tissues, with a high correlation between the histological grade and prognosis. Knockdown of Txl-2 expression significantly inhibited cancer cell motility, and the invasive and metastatic abilities of colon cancer cells. Interestingly, Txl-2 isoforms showed differential effects on cancer cell invasion and metastasis. Cell invasion and metastasis were significantly promoted by Txl-2b but inhibited by Txl-2c, while no obvious effect was observed for Txl-2a. Furthermore, a direct interaction was identified between Txl-2b and Ran, a Ras-related protein, by yeast two-hybrid assay and coimmunoprecipitation. PI3K pathway was found to be a major pathway mediating Txl-2b induced tumor invasion and metastasis.
  
  
  METHODS
  The current study provides a novel biomarker and target molecule for the diagnosis and treatment of colon cancer and provides a novel paradigm to understand how alternative splicing functions in human cancer.
  
  
  CONCLUSIONS
  Our findings demonstrate an elevated Txl-2 expression in colon cancer and that Txl-2b promotes cell invasion and metastasis through interaction with Ran and PI3K signaling pathway.
authors: State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
authors: Yuanyuan
authors: Y
authors: Lu
authors: Xiaodi
authors: X
authors: Zhao
authors: Kai
authors: K
authors: Li
authors: Guanhong
authors: G
authors: Luo
authors: Yongzhan
authors: Y
authors: Nie
authors: Yongquan
authors: Y
authors: Shi
authors: Yi
authors: Y
authors: Zhou
authors: Gui
authors: G
authors: Ren
authors: Bin
authors: B
authors: Feng
authors: Zhenxiong
authors: Z
authors: Liu
authors: Yan
authors: Y
authors: Pan
authors: Ting
authors: T
authors: Li
authors: Xuegang
authors: X
authors: Guo
authors: Kaichun
authors: K
authors: Wu
authors: Antonio
authors: A
authors: Miranda-Vizuete
authors: Xin
authors: X
authors: Wang
authors: Daiming
authors: D
authors: Fan
mesh_terms: D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D023061:Gene Order; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D011485:Protein Binding; D020033:Protein Isoforms; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D020931:ran GTP-Binding Protein / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C404105:GLRX3 protein, human; D020033:Protein Isoforms; C120587:RAN protein, human; D051057:Proto-Oncogene Proteins c-akt; D020782:Matrix Metalloproteinases; D020931:ran GTP-Binding Protein