Related Experiment Video

Updated: Mar 30, 2026

The Soft Agar Colony Formation Assay
08:01

The Soft Agar Colony Formation Assay

Published on: October 27, 2014

114.4K

TGIF function in oncogenic Wnt signaling

Mohammed S Razzaque1, Azeddine Atfi2

  • 1Department 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.

Biochimica Et Biophysica Acta
|November 3, 2015
PubMed

Insights

Transforming growth-interacting factor (TGIF) drives cancer by hijacking Wnt/β-catenin signaling. It sequesters key proteins in the nucleus, boosting β-catenin and promoting tumor growth, particularly in triple-negative breast cancer (TNBC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling Pathways

Background:

  • Transforming growth-interacting factor (TGIF) is linked to human cancer pathogenesis.
  • The precise mechanisms of TGIF's role in cancer remain largely unknown.

Purpose of the Study:

  • To elucidate the role of TGIF in mediating oncogenic Wnt/β-catenin signaling.
  • To investigate TGIF's impact on cancer progression and patient prognosis.

Main Methods:

  • Investigated TGIF's interaction with Axin1 and Axin2.
  • Analyzed the effect of TGIF on the β-catenin-destruction complex.
  • Assessed TGIF expression levels in triple-negative breast cancer (TNBC) patient samples.
  • Evaluated TGIF's role in mammary tumorigenesis in vivo.

Main Results:

  • TGIF interacts with and sequesters Axin1 and Axin2 in the nucleus.
  • This sequestration leads to the disassembly of the β-catenin-destruction complex.
  • Nuclear accumulation of β-catenin activates Wnt target genes, including TGIF itself.
  • High TGIF expression correlates with poor prognosis in TNBC patients.
  • TGIF promotes Wnt-driven mammary tumorigenesis in vivo.

Conclusions:

  • TGIF acts as a crucial mediator of oncogenic Wnt/β-catenin signaling.
  • TGIF promotes tumorigenesis by stabilizing β-catenin and activating Wnt target genes.
  • TGIF is a potential prognostic marker and therapeutic target for TNBC.
Keywords:
Axin1Axin2Mammary tumorTGIFβ-Catenin

More Related Videos

Modeling Paracrine Noncanonical Wnt Signaling In Vitro11:14

Modeling Paracrine Noncanonical Wnt Signaling In Vitro

Published on: December 10, 2021

2.0K
Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis09:58

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis

Published on: June 27, 2020

3.2K

Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
10.9K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

2.6K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
8.6K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

1.9K
Catenins01:23

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
3.3K
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.9K