Background. Loss ofLLGL1has been associated with loss of cellular adhesion and dissemination of cells from colorectal cancer and malignant melanoma. Regulation and relevance ofLLGL1were analyzed in gastric cancer patients with lymphatic and distant dissemination. Furthermore,LLGL1expression was analyzed in relation to the cellular adhesion proteinE-cadherin.Methods.LLGL1andE-cadherintranscription levels were evaluated in 56 gastric cancer patients and five gastric cancer cell lines. IHC staining forLLGL1was performed on 39 gastric cancer specimens.LLGL1was stably transfected intoLLGL1negative gastric cancer cell line SNU16 (del(17) (p11.2)) for functionalin vitroassays and a xenograft bioassay.Results. Gastric cancer specimens and cell lines displayedLLGL1andE-cadherinexpression levels with variable intensity. In gastric mucosa,LLGL1exhibited weak cytoplasmic and strong cortical staining. Loss ofLLGL1expression occurred in 65% of gastric cancers and significantly correlated with loss ofE-cadherinexpression (P=0.00009). Loss ofLLGL1expression was associated with the diffuse type of gastric cancer (P=0.029) with peritoneal carcinomatosis (M1; P=0.006) and with female gender (P=0.017). Stable reexpression ofLLGL1in SNU16 cells significantly increased both plastic surface adhesion and extracellular matrix proteins laminin and fibronectin, but had no impact onin vitroproliferation, apoptosis, or invasion or onin vivoproliferation or differentiation in our xenograft bioassay.Conclusion.LLGL1is coexpressed withE-cadherin.Loss of expression of either protein is associated with diffuse gastric cancer and peritoneal metastases.LLGL1does not impact on proliferation or epithelial-mesenchymal transition (EMT) rather increasing cellular adhesion.
E-Cadherin (CDH1) and p53 rather than SMAD4 and Caspase-10 germline mutations contribute to genetic predisposition in Portuguese gastric cancer patients