title: TGIF governs a feed-forward network that empowers Wnt signaling to drive mammary tumorigenesis.
abstract: Many types of human cancers having hyperactivated Wnt signaling display no causative alterations in known effectors of this pathway. Here, we report a function of TGIF in Wnt signaling. TGIF associates with and diverts Axin1 and Axin2 from the β-catenin destruction complex, therefore allowing β-catenin accrual. Intriguingly, activation of Wnt signaling induces the expression of TGIF, which unveils a feed-forward loop that ensures effective integration of Wnt signaling. In triple-negative breast cancers (TNBC), elevated levels of TGIF correlate with high Wnt signaling and poor survival of patients. Moreover, genetic experiments revealed that Tgif1 ablation impeded mammary tumor development in MMTV-Wnt1 mice, further underscoring a requirement of TGIF for oncogenic Wnt signaling.
authors: Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA; Department of Orthopaedics, Tongji University School of Medicine, Shanghai 200065, China.
authors: Ming-Zhu
authors: MZ
authors: Zhang
authors: Laboratory of Cell Signaling and Carcinogenesis, INSERM UMRS938, 184 Rue du Faubourg St-Antoine, 75571 Paris, France.
authors: Olivier
authors: O
authors: Ferrigno
authors: Department of Biochemistry, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
authors: Zhe
authors: Z
authors: Wang
authors: Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA.
authors: Mutsuko
authors: M
authors: Ohnishi
authors: Laboratory of Cell Signaling and Carcinogenesis, INSERM UMRS938, 184 Rue du Faubourg St-Antoine, 75571 Paris, France.
authors: Céline
authors: C
authors: Prunier
authors: Laboratory of Cell Signaling and Carcinogenesis, INSERM UMRS938, 184 Rue du Faubourg St-Antoine, 75571 Paris, France.
authors: Laurence
authors: L
authors: Levy
authors: Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA.
authors: Mohammed
authors: M
authors: Razzaque
authors: Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA.
authors: Williams C
authors: WC
authors: Horne
authors: Department of Biochemistry, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
authors: Damian
authors: D
authors: Romero
authors: Department of Biochemistry, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
authors: Guri
authors: G
authors: Tzivion
authors: Hybrigenics, 3-5 impasse Reille, 75014 Paris, France.
authors: Frédéric
authors: F
authors: Colland
authors: Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA.
authors: Roland
authors: R
authors: Baron
authors: Laboratory of Cell Signaling and Carcinogenesis, INSERM UMRS938, 184 Rue du Faubourg St-Antoine, 75571 Paris, France; Department of Biochemistry, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. Electronic address: azeddine.atfi@inserm.fr.
authors: Azeddine
authors: A
authors: Atfi
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D060466:Axin Protein / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D060466:Axin Protein; C555452:Axin1 protein, mouse; C111729:Axin2 protein, mouse; D018398:Homeodomain Proteins; D012097:Repressor Proteins; C490797:Tgif1 protein, mouse; D051176:beta Catenin