title: TGIF function in oncogenic Wnt signaling.
abstract: Transforming growth-interacting factor (TGIF) has been implicated in the pathogenesis of many types of human cancer, but the underlying mechanisms remained mostly enigmatic. Our recent study has revealed that TGIF functions as a mediator of oncogenic Wnt/β-catenin signaling. We found that TGIF can interact with and sequesters Axin1 and Axin2 into the nucleus, thereby culminating in disassembly of the β-catenin-destruction complex and attendant accumulation of β-catenin in the nucleus, where it activates expression of Wnt target genes, including TGIF itself. We have provided proof-of-concept evidences that high levels of TGIF expression correlate with poor prognosis in patients with triple negative breast cancer (TNBC), and that TGIF empowers Wnt-driven mammary tumorigenesis in vivo. Here, we will briefly summarize how TGIF influences Wnt signaling to promote tumorigenesis.
authors.affiliation: Department of Applied Oral Sciences, The Forsyth Institute, Harvard School of Dental Medicine Affiliate, 245 First Street, Cambridge, MA 02142, USA; Department of Pathology, Saba University School of Medicine, Church Street, Saba, Dutch Caribbean. Electronic address: mrazzaque@forsyth.org.
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Razzaque
authors.affiliation: Cancer Institute and Department of Biochemistry, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA; INSERM UMRS 938, Laboratory of Cell Signaling and Carcinogenesis, Hôpital Saint-Antoine, 34 rue Crozatier, 75012 Paris, France.
authors.forename: Azeddine
authors.initials: A
authors.lastname: Atfi
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000209:etiology*; D005260:Female; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D012097:Repressor Proteins / Q000502:physiology*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology
chemical_list: D018398:Homeodomain Proteins; D012097:Repressor Proteins; C097504:TGIF1 protein, human; D051176:beta Catenin
keywords: Axin1; Axin2; Mammary tumor; TGIF; β-Catenin