Abstract
BackgroundForkhead box L1 (FOXL1), considered as a novel candidate tumor suppressor, suppresses proliferation and invasion in certain cancers. However, the regulation and function of FOXL1 in gallbladder cancer (GBC) remains unclear.MethodsFOXL1 expression at mRNA and protein levels in GBC tissues and cell lines were examined by RT-PCR, immunohistochemistry and western blot assay. FOXL1 expression in GBC cell lines was up-regulated by transfection with pcDNA-FOXL1. The effects of FOXL1 overexpression on cell proliferation, apoptosis, migration and invasion were evaluated in vitro or in vivo. In addition, the status of mediators involved in migration, invasion and apoptosis was examined using western blot after transfection with pcDNA-FOXL1.ResultsFOXL1 was frequently downregulated in GBC tissues and cell lines. Its higher expression is associated with better prognosis, while its lower expression is correlated with advanced TNM stage and poor differentiation. FOXL1 overexpression in NOZ cells significantly suppresses cell proliferation, migration and invasion in vitro and tumorigenicity in nude mice. FOXL1 overexpression disrupted mitochondrial transmembrane potential and triggered mitochondria-mediated apoptosis in NOZ cells. In addition, FOXL1 overexpression suppressed ZEB1 expression and induced E-cadherin expression in NOZ cells.ConclusionOur findings suggested that dysregulated FOXL1 is involved in tumorigenesis and progression of GBC and may serve as a predictor of clinical outcome or even a therapeutic target for patients with GBC.
Highlights
Gallbladder cancer (GBC) which represents the most common and aggressive type among biliary tract malignancies is characterized by non-specific presentation, late diagnosis and lack of effective treatment
We investigated the significance of Forkhead box L1 (FOXL1) expression in patients with gallbladder cancer (GBC) in relation to clinical features and prognosis
FOXL1 mRNA and protein were examined in tumor tissues and nontumor tissues by RT-PCR, western blot and immunohistochemistry analysis, respectively
Summary
Gallbladder cancer (GBC) which represents the most common and aggressive type among biliary tract malignancies is characterized by non-specific presentation, late diagnosis and lack of effective treatment. Recent advances have been made in the diagnosis and treatment, the outcomes of current therapies, such as surgery, chemotherapy and radiotherapy (alone or combined) have been proven to be dismal. It is associated with a poor prognosis with median survival duration of 4 months [1] and 5-year survival rate less than 10% [2]. There is an urgent need to develop novel and effective therapy regimens for GBC patients. The limited knowledge on tumorigenesis of gallbladder cancer hinders the development of diagnosis and treatment for GBC. The regulation and function of FOXL1 in gallbladder cancer (GBC) remains unclear
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