CYLD deficiency promotes pancreatic cancer development by causing mitotic defects |
| |
Authors: | Songbo Xie Yuhan Wu Huijie Hao Jingrui Li Song Guo Wei Xie Dengwen Li Jun Zhou Jinmin Gao Min Liu |
| |
Institution: | 1. College of Life Sciences, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Institute of Biomedical Sciences, Shandong Normal University, Jinan, Shandong, China;2. State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of the Ministry of Education, Tianjin Key Laboratory of Protein Science, College of Life Sciences, Nankai University, Tianjin, China |
| |
Abstract: | Successful treatment of pancreatic cancer, which has the highest mortality rate among all types of malignancies, has challenged oncologists for decades, and early detection would undoubtedly increase favorable patient outcomes. The identification of proteins involved in pancreatic cancer progression could lead to biomarkers for early detection of this disease. This study identifies one potential candidate, cylindromatosis (CYLD), a deubiquitinase and microtubule-binding protein that plays a suppressive role in pancreatic cancer development. In pancreatic cancer samples, downregulation of CYLD expression resulted from a loss in the copy number of the CYLD gene; additionally, reduced expression of CYLD negatively correlated with the clinicopathological parameters. Further study demonstrated that CYLD deficiency promoted colony formation in vitro and pancreatic cancer growth in vivo. Mechanistic studies revealed that CYLD is essential for spindle orientation and properly oriented cell division; CYLD deficiency resulted in a substantial increase in chromosome missegregation. Taken together, these data indicate a critical role for CYLD in suppressing pancreatic tumorigenesis, implicating its potential as a biomarker for early detection of pancreatic cancer and a prognostic indicator of patient outcomes. |
| |
Keywords: | chromosome missegregation cylindromatosis (CYLD) pancreatic cancer spindle misorientation tumorigenesis |
|
|