title: Ahnak functions as a tumor suppressor via modulation of TGFβ/Smad signaling pathway.
abstract: We provide detailed mechanisms of Ahnak-mediated potentiation of transforming growth factor β (TGFβ) signaling, which leads to a negative regulation of cell growth. We show that Smad3 interacts with Ahnak through MH2 domain and that Ahnak stimulates Smad3 localization into nucleus leading to potentiating TGFβ-induced transcriptional activity of R-Smad. Moreover, overexpression of Ahnak resulted in growth retardation and cell cycle arrest through downregulation of c-Myc and cyclin D1/D2. We describe results from analyses of Ahnak(-/-) mouse model expressing middle T antigen in a mammary gland-specific manner (MMTV(Tg/+)Ahnak(-/-)), which showed significantly progressed hyperplasia of mammary glands compared with MMTV(Tg/+)Ahnak(+/+). Finally, we screened multiple human breast cancer tissues and showed that the expression of Ahnak in cancer tissues is lower than that in control tissues by 50%. Taken together, these data indicate that Ahnak mediates a negative regulation of cell growth and acts as novel tumor suppressor through potentiation of TGFβ signaling.
authors.affiliation: Department of Life Sciences and GT5 program, Ewha Womans University, Seoul, Korea.
authors.forename: I H
authors.initials: IH
authors.lastname: Lee
authors.affiliation: Department of Life Sciences and GT5 program, Ewha Womans University, Seoul, Korea.
authors.forename: M
authors.initials: M
authors.lastname: Sohn
authors.affiliation: Department of Life Sciences and GT5 program, Ewha Womans University, Seoul, Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Lim
authors.affiliation: Department of Life Sciences and GT5 program, Ewha Womans University, Seoul, Korea.
authors.forename: S
authors.initials: S
authors.lastname: Yoon
authors.affiliation: Department of Life Sciences and GT5 program, Ewha Womans University, Seoul, Korea.
authors.forename: H
authors.initials: H
authors.lastname: Oh
authors.affiliation: Department of Life Sciences and GT5 program, Ewha Womans University, Seoul, Korea.
authors.forename: S
authors.initials: S
authors.lastname: Shin
authors.affiliation: Laboratory of Developmental Biology and Genomics, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Shin
authors.affiliation: College of Pharmacy, Gachon University, Incheon, Korea.
authors.forename: S-H
authors.initials: SH
authors.lastname: Oh
authors.affiliation: Department of Life Sciences and GT5 program, Ewha Womans University, Seoul, Korea.
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Life Sciences and GT5 program, Ewha Womans University, Seoul, Korea.
authors.forename: D K
authors.initials: DK
authors.lastname: Lee
authors.affiliation: Department of Surgery, School of Medicine, Seoul National University, Seoul, Korea.
authors.forename: D Y
authors.initials: DY
authors.lastname: Noh
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Hospital, SungKyunKwan University, Seoul, Korea.
authors.forename: D S
authors.initials: DS
authors.lastname: Bae
authors.affiliation: Laboratory of Developmental Biology and Genomics, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
authors.forename: J K
authors.initials: JK
authors.lastname: Seong
authors.affiliation: Department of Life Sciences and GT5 program, Ewha Womans University, Seoul, Korea.
authors.forename: Y S
authors.initials: YS
authors.lastname: Bae
mesh_terms: D000818:Animals; D019556:COS Cells; D059447:Cell Cycle Checkpoints; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000502:physiology*; D009368:Neoplasm Transplantation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000502:physiology
chemical_list: C489572:Ahnak protein, mouse; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I