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

Cancer cell 2015 Apr 13

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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. Copyright © 2015 Elsevier Inc. All rights reserved.

Citation

Ming-Zhu Zhang, Olivier Ferrigno, Zhe Wang, Mutsuko Ohnishi, Céline Prunier, Laurence Levy, Mohammed Razzaque, Williams C Horne, Damian Romero, Guri Tzivion, Frédéric Colland, Roland Baron, Azeddine Atfi. TGIF governs a feed-forward network that empowers Wnt signaling to drive mammary tumorigenesis. Cancer cell. 2015 Apr 13;27(4):547-60