title: Activin type IB receptor signaling in prostate cancer cells promotes lymph node metastasis in a xenograft model.
abstract: Activin, a member of the transforming growth factor-β family, has been known to be a growth and differentiating factor. Despite its pluripotent effects, the roles of activin signaling in prostate cancer pathogenesis are still unclear. In this study, we established several cell lines that express a constitutive active form of activin type IB receptor (ActRIBCA) in human prostate cancer cells, ALVA41 (ALVA-ActRIBCA). There was no apparent change in the proliferation of ALVA-ActRIBCA cells in vitro; however, their migratory ability was significantly enhanced. In a xenograft model, histological analysis revealed that the expression of Snail, a cell-adhesion-suppressing transcription factor, was dramatically increased in ALVA-ActRIBCA tumors, indicating epithelial mesenchymal transition (EMT). Finally, mice bearing ALVA-ActRIBCA cells developed multiple lymph node metastases. In this study, we demonstrated that ActRIBCA signaling can promote cell migration in prostate cancer cells via a network of signaling molecules that work together to trigger the process of EMT, and thereby aid in the aggressiveness and progression of prostate cancers.
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. nomura@med.kyushu-u.ac.jp
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nomura
authors.forename: Kimitaka
authors.initials: K
authors.lastname: Tanaka
authors.forename: Lixiang
authors.initials: L
authors.lastname: Wang
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Goto
authors.forename: Chizu
authors.initials: C
authors.lastname: Mukasa
authors.forename: Kenji
authors.initials: K
authors.lastname: Ashida
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takayanagi
mesh_terms: D030201:Activin Receptors, Type I / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C498932:ACVR1B protein, human; D030201:Activin Receptors, Type I