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Transient gene silencing of galectin-3 suppresses pancreatic cancer cell migration and invasion through degradation of ?-catenin.


ABSTRACT: Pancreatic cancer is a leading cause of cancer-related mortality and often has a poor prognosis because of its late diagnosis, aggressive local invasion, early metastasis and poor response to chemotherapy. The chemotherapeutic agent gemcitabine is effective for treating advanced pancreatic cancer, but its efficacy remains less than satisfactory. It is expected that further investigation of pancreatic cancer cell invasion and development of strategies to block this process should improve the disease prognosis. In this study, we tested our hypothesis that galectin-3 (gal-3), a multifunctional member of the ?-galactoside-binding protein family, may regulate pancreatic cancer cell motility and silencing of it inhibit cell motility. Previous studies demonstrated that this protein is associated with tumor cell adhesion, proliferation, differentiation, angiogenesis, apoptosis and metastasis. Here, we used gal-3 small interfering RNA (siRNA) to silence its expression in various pancreatic cancer cell lines to determine whether gal-3 regulates cell proliferation, migration and invasion in vitro. We found that silencing gal-3 reduced cellular migration and invasion, but failed to affect proliferation. In gal-3 siRNA-transfected cells, we detected a decrease in ?-catenin expression, an important signal for cancer cell invasion, which was caused by downregulation of phosphorylated Akt and GSK-3?. We also found that matrix metalloproteinase (MMP)-2 expression was reduced by gal-3 silencing. These results indicate that gal-3-mediated invasion via MMP-2 regulated by ?-catenin degradation is initiated by Akt phosphorylation in pancreatic cancer cells. Our results suggest that gal-3 can be a novel therapeutic target in pancreatic cancer.

SUBMITTER: Kobayashi T 

PROVIDER: S-EPMC3833077 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Transient gene silencing of galectin-3 suppresses pancreatic cancer cell migration and invasion through degradation of β-catenin.

Kobayashi Tsutomu T   Shimura Tatsuo T   Yajima Toshiki T   Kubo Norio N   Araki Kenichiro K   Tsutsumi Soichi S   Suzuki Hideki H   Kuwano Hiroyuki H   Raz Avraham A  

International journal of cancer 20110329 12


Pancreatic cancer is a leading cause of cancer-related mortality and often has a poor prognosis because of its late diagnosis, aggressive local invasion, early metastasis and poor response to chemotherapy. The chemotherapeutic agent gemcitabine is effective for treating advanced pancreatic cancer, but its efficacy remains less than satisfactory. It is expected that further investigation of pancreatic cancer cell invasion and development of strategies to block this process should improve the dise  ...[more]

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