Wwox suppresses breast cancer cell growth through modulation of the hedgehog-GLI1 signaling pathway

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• 作者：Anwen Xiong ; Li Wei ; Mingzhen Ying ; Hongmei Wu ; Jin Hua ; Yajie Wang
• 关键词：Breast cancer ; Wwox ; Gli1 ; Hedgehog
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：24 January, 2014
• 年：2014
• 卷：443
• 期：4
• 页码：1200-1205
• 全文大小：943 K

文摘

Wwox is a tumor suppressor that is frequently deleted or altered in several cancer types, including breast cancer. Previous studies have shown that ectopic expression of Wwox inhibits proliferation of breast cancer cells. However, the underlying mechanism remains unclear. To better understand the molecular mechanisms of Wwox function, we investigated novel partners of this protein. Utilizing the coimmunoprecipitation assay, we observed a physical association between Wwox and the Gli1 zinc-finger transcription factor involved in the hedgehog pathway. Our results further demonstrated that Wwox expression triggered redistribution of nuclear Gli1 to the cytoplasm. Additionally, ectopic expression of Wwox reduced Gli1 expression in vitro. Furthermore, Gli1 Blocks Wwox-induced breast cancer cell growth inhibition. These findings suggest a functional crosstalk between Wwox and hedgehog-GLI1 signaling pathway in tumorigenesis.