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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 ?-catenin destruction complex, therefore allowing ?-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.

SUBMITTER: Zhang MZ

PROVIDER: S-EPMC4398914 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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

Zhang Ming-Zhu MZ Ferrigno Olivier O Wang Zhe Z Ohnishi Mutsuko M Prunier Céline C Levy Laurence L Razzaque Mohammed M Horne Williams C WC Romero Damian D Tzivion Guri G Colland Frédéric F Baron Roland R Atfi Azeddine A

Cancer cell 20150401 4

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 ...[more]

PMID: 25873176

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