title: Lung metastasis of pancreatic carcinoma is regulated by TGFβ signaling.
abstract: The molecular regulation of the lung metastasis of pancreatic carcinoma (PCC) is not completely understood. Here, we show that the levels of phosphorylated SMAD3, ZEB1, ZEB2, Snail1, and Snail2 were significantly higher in PCC with lung metastasis than in PCC without lung metastasis. Overexpression of TGFβ1 enhanced the invasiveness of PCC cells, while inhibition of TGFβ1 decreased the invasiveness of PCC cells, which appeared to be conducted by activated TGFβ receptor signaling-induced upregulation of ZEB1, ZEB2, Snail1, and Snail2, suggesting a process of epithelial-mesenchymal transition (EMT). Taken together, our study provides evidence that TGFβ receptor signaling-induced EMT may be responsible for the increased PCC invasiveness to enhance its lung metastasis.
authors.affiliation: Department of Pathology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dongdansantiao, 100005, Beijing, China, liqiang_song@163.com.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Song
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Tian
authors.forename: De
authors.initials: D
authors.lastname: Chang
authors.forename: Kailong
authors.initials: K
authors.lastname: Li
authors.forename: Yongna
authors.initials: Y
authors.lastname: Fan
authors.forename: Jing
authors.initials: J
authors.lastname: Shen
authors.forename: Hongzhen
authors.initials: H
authors.lastname: Du
authors.forename: Ruifang
authors.initials: R
authors.lastname: Mi
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Bian
authors.forename: Xianchao
authors.initials: X
authors.lastname: Tang
mesh_terms: D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012097:Repressor Proteins / Q000096:biosynthesis; D015398:Signal Transduction; D051900:Smad3 Protein / Q000096:biosynthesis; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D018398:Homeodomain Proteins; D012097:Repressor Proteins; C497790:SMAD3 protein, human; C000604407:SNAI1 protein, human; D051900:Smad3 Protein; D000071250:Snail Family Transcription Factors; C508960:TGFB1 protein, human; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; C486307:ZEB1 protein, human; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1