title: FOXO3a promotes gastric cancer cell migration and invasion through the induction of cathepsin L.
abstract: Forkhead box O3A (FOXO3a) is an important transcription factor involved in various human cancers. However, the role of FOXO3a in regulating the invasion and metastasis of gastric cancer cells has not been clarified. Here, we report that FOXO3a overexpression promoted migration and invasion of gastric cancer cells by upregulating cathepsin L. FOXO3a knockdown suppressed migration and invasion and also downregulated cathepsin L expression in gastric cancer cells. Silencing cathepsin L in these cells suppressed FOXO3a overexpression-induced cell migration and invasion. Mechanistic studies revealed that FOXO3a increased cathepsin L promoter activation, and cathepsin L overexpression repressed E-cadherin expression, causing gastric cancer cells to undergo epithelial-mesenchymal transition (EMT). Our data reveal a previously unexplored function of FOXO3a in gastric cancer invasion by regulating proteins involved in extracellular matrix (ECM) degradation and EMT. We suggest that FOXO3a may be of prognostic value and a potential therapeutic target in blocking tumor metastasis.
authors.affiliation: Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
authors.forename: Shan
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Department of Biostatistics, Fudan University, Shanghai, People's Republic of China.
authors.forename: Naiqing
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
authors.forename: Yihong
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
authors.forename: Tianshu
authors.initials: T
authors.lastname: Liu
mesh_terms: D015820:Cadherins / Q000096:biosynthesis; D056668:Cathepsin L / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism*; D000071316:Forkhead Box Protein O3 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D015820:Cadherins; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D056668:Cathepsin L
keywords: FOXO3a; cathepsin L; gastric cancer migration; invasion