title: Leptin-mediated regulation of ICAM-1 is Rho/ROCK dependent and enhances gastric cancer cell migration.
abstract: BACKGROUND
  Our previous study indicates that leptin enhances gastric cancer (GC) invasion. However, the exact effect of leptin on GC metastasis and its underlying mechanism remain unclear. Intercellular adhesion molecule-1 (ICAM-1), a major molecule in stabilising cell-cell and cell-extracellular matrix interactions, is overexpressed and has crucial roles in tumour metastasis.
  
  
  METHODS
  Here, we investigated leptin and ICAM-1 expression in GC tissues. Furthermore, we characterised the influence of leptin on ICAM-1 expression in GC cells and elucidated the underlying mechanism.
  
  
  RESULTS
  Leptin and ICAM-1 were overexpressed in GC tissues, and a strong positive correlation was observed. They were also related with clinical stage or lymph node metastasis. Furthermore, leptin induced GC cell (AGS and MKN-45) migration by upregulating ICAM-1, and knockdown of ICAM-1 by small interference RNA (siRNA) blocked this process. Cell surface ICAM-1, as well as soluble ICAM-1 (sICAM-1), was also enhanced by leptin. Moreover, leptin increased ICAM-1 expression through Rho/ROCK pathway, which was attenuated by pharmacological inhibition of Rho (C3 transferase) or its downstream effector kinase Rho-associated protein kinase (ROCK) (Y-27632).
  
  
  CONCLUSIONS
  Our findings indicate that leptin enhances GC cell migration by increasing ICAM-1 through Rho/ROCK pathway, which might provide new insight into the significance of leptin in GC.
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan 250012, Shandong, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan 250012, Shandong, China.
authors.forename: S
authors.initials: S
authors.lastname: Fu
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan 250012, Shandong, China.
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan 250012, Shandong, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan 250012, Shandong, China.
authors.forename: L
authors.initials: L
authors.lastname: Du
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan 250012, Shandong, China.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan 250012, Shandong, China.
authors.forename: S
authors.initials: S
authors.lastname: Kan
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan 250012, Shandong, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan 250012, Shandong, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan 250012, Shandong, China.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan 250012, Shandong, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan 250012, Shandong, China.
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.affiliation: Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan 250012, Shandong, China.
authors.forename: X
authors.initials: X
authors.lastname: Qu
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan 250012, Shandong, China.
authors.forename: C
authors.initials: C
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D020738:Leptin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured; D020741:rho GTP-Binding Proteins / Q000502:physiology*; D054460:rho-Associated Kinases / Q000502:physiology*
chemical_list: D020738:Leptin; D018799:Intercellular Adhesion Molecule-1; D054460:rho-Associated Kinases; D020741:rho GTP-Binding Proteins