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Zyxin as a potential cancer prognostic marker promotes the proliferation and metastasis of colorectal cancer cells |
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| Authors: | Chenhan Zhong Jiekai Yu Dan Li Kai Jiang Yang Tang Mengyuan Yang Hong Shen Xuefeng Fang Kefeng Ding Shu Zheng Ying Yuan |
| Institution: | 1. Department of Medical Oncology, (Key Laboratory of Cancer Prevention and Intervention, Chinese National Ministry of Education;2. Key Laboratory of Molecular Biology in Medical Sciences) The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
Zhong and Yu have contributed equally to this study.;3. Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China Zhong and Yu have contributed equally to this study.;4. Key Laboratory of Molecular Biology in Medical Sciences) The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China;5. Department of Surgical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China;6. Cancer Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China Research Center for Air Pollution and Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China |
| Abstract: | Colorectal cancer (CRC) is a leading cause of cancer death. This study was conducted to investigate the functions and mechanisms of Zyxin (ZYX) in CRC. Multiomics analysis associated ZYX with CRC metastasis. ZYX expression levels were increased in human CRC tissues and related to shorter recurrence-free survival. Knockdown of ZYX expression resulted in inhibition of cell growth, invasion, and migration in vitro and in vivo. Comprehensive analysis of gene microarray analysis showed that ZYX may activate the pathway of NUPR1 and JNK, inhibit CST5, regulate focal adhesion (FA), and affect epithelial–mesenchymal transition in CRC cells. Results of gene microarray and membrane protein isobaric tags with relative and absolute quantitation labeling mass spectrometry found ten differentially expressed genes, which were associated with ZYX activity. Furthermore, real-time polymerase chain reaction was used to validate the expression patterns of selected genes in the integrative analysis. Taken together, our findings provide the first evidence that decreased expression level of ZYX impairs CRC cell proliferation and metastasis probably via the FA pathway. |
| Keywords: | colorectal cancer focal adhesion metastasis proliferation Zyxin |