WW45 inhibits breast cancer cell proliferation by the Hedgehog signaling pathway

作者：Xiong, Anwen; Li, Lin; Li, Wei; Yu, Jia; Lian, Zhengjun; Zhang, Ziyu; Luo, Rongcheng^*

来源：American Journal of Translational Research, 2021, 13(4): 2617-2625.

• Breast cancer
• WW45
• Gli1
• hedgehog

WW45 is a recently-discovered tumor suppressor gene. Overexpression of WW45 was found to significantly weaken proliferation and colony formation in a human breast cancer cell line, but the molecular mechanism of WW45's inhibitiory effect on proliferation was uncertain. It is a key transcription factor of the Hedgehog signaling pathway. In particular, the mechanism of Gilts upstream proteins in regulating Gill's nuclear import was not clear. We collected different breast cancer cell lines and detected WW45 and Glil expression by western blot. Glil expression was detected after WW45 was overexpressed in breast cancer cells. Glil and WW45 were transfected into breast cancer cells, and co-immunoprecipitation was used to detect whether the two proteins had physical interaction. We confirmed Glil blocks WW45-induced growth inhibition and colony formation in ZR-75-30 cells through cell functional experiments. Expression of VW/45 negatively correlated with Glil expression in breast cancer cells. WW45 affected Glil intracellular localization though ww-PPxY/PsP interaction. Glil blocked WW45-induced growth inhibition and colony formation in ZR-75-30 cells. Our results strongly suggest that expression of WW45 negatively correlates with Glil expression in breast cancer cells. direct physical interaction occurred between WW45 and Glil, and WW45 affected Glil intracellular localization though WW-PPxY/PsP interaction. Furthermore, Glil blocked WW45-induced breast cancer cell growth inhibition.

• 单位
  南方医科大学; 同济大学