TGIF governs a feed-forward network that empowers Wnt signaling to drive mammary tumorigenesis.

Cancer Cell

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:

Published: April 2015

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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4398914PMC
http://dx.doi.org/10.1016/j.ccell.2015.03.002DOI Listing

Publication Analysis

Top Keywords

wnt signaling
28
wnt
7
signaling
7
tgif
6
tgif governs
4
governs feed-forward
4
feed-forward network
4
network empowers
4
empowers wnt
4
signaling drive
4

Similar Publications

Glioma is a highly aggressive and invasive brain tumor with limited treatment options, highlighting the need for novel therapeutic approaches. Kinesin superfamily proteins (KIFs) are a diverse group of motor proteins that play essential roles in cellular processes such as mitosis, intracellular transport, and signal transduction, all of which are crucial for tumorigenesis. This review focuses on the multifaceted role of KIFs in glioma, examining their clinical relevance, contribution to tumor progression, and potential as therapeutic targets.

View Article and Find Full Text PDF

A 29-year-old Spanish Caucasian man, without relevant family history, was attended in our unit due to an undiagnosed skeletal dysplasia associated with low bone mass and several fragility fractures throughout his childhood and adolescence. DXA exams throughout his life showed very low BMD values; currently, his spinal and femoral neck T-scores were - 4.3 and - 3.

View Article and Find Full Text PDF

: Asthenozoospermia, characterized by reduced sperm motility, is a common cause of male infertility. Emerging evidence suggests that noncoding RNAs, particularly long noncoding RNAs (lncRNAs), play a critical role in the regulation of spermatogenesis and sperm function. Coding regions have a well-characterized role and established predictive value in asthenozoospermia.

View Article and Find Full Text PDF

Bone defects caused by fractures and diseases often do not heal spontaneously. They require external agents for repair and regeneration. Bone tissue engineering is emerging as a promising alternative to traditional therapies like autografts and allografts.

View Article and Find Full Text PDF

Background: Uremia (UR) is caused by increased UR-related toxins in the bloodstream. We explored the mechanism of enterogenous toxin methylmalonic acid (MMA) in calcium-phosphorus metabolic disorder in UR rats via the Wnt/β-catenin pathway.

Methods: The UR rat model was established by 5/6 nephrectomy.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!