NUDCD1 promotes metastasis through inducing EMT and inhibiting apoptosis in colorectal cancer

Bin Han; Yuan-Yuan Zhang; Ke Xu; Yang Bai; Li-Hong Wan; Shi-Kun Miao; Ke-Xian Zhang; Hong-Wei Zhang; Yin Liu; Li-Ming Zhou

NUDCD1 promotes metastasis through inducing EMT and inhibiting apoptosis in colorectal cancer

Am J Cancer Res. 2018 May 1;8(5):810-823. eCollection 2018.

Authors

Bin Han^{1

2}, Yuan-Yuan Zhang¹, Ke Xu¹, Yang Bai¹, Li-Hong Wan¹, Shi-Kun Miao¹, Ke-Xian Zhang³, Hong-Wei Zhang³, Yin Liu^{1

3}, Li-Ming Zhou¹

Affiliations

¹ Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University Chengdu 610041, Sichuan Province, China.
² Department of Pharmacy, Affiliated Hospital of North Sichuan Medical College Nanchong 637000, Sichuan Province, China.
³ Department of Anesthesiology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China Chengdu 610041, Sichuan Province, China.

PMID: 29888104
PMCID: PMC5992514

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the third leading cause of cancer death in both men and women. NudC domain containing 1 (NUDCD1) was identified as an oncoprotein which was activated or over-expressed in various human cancers. We aimed to investigate the effects and mechanisms of NUDCD1 in human CRC. The expression of NUDCD1 in CRC and pericarcinous tissues from 70 CRC patients were determined by real-time PCR, western blotting, and immunohistochemistry. The correlation between the expression of NUDCD1 and clinical characteristics was analyzed. The expression of NUDCD1 in five CRC cell lines and normal colon mucosal epithelial cell line was measured by real-time PCR. Then we knock down NUDCD1 in HCT116 and HT 29 cells. The cell viability assay, scratch assay, migration and invasion assay and flow cytometry were used to analyze NUDCD1's effects on the proliferation, migration, invasion, cell cycle and apoptosis of CRC cells. NUDCD1's effects on CRC xenografts of nude mice was also determined. Results showed that the expression of NUDCD1 was much higher in CRC tissues than that in pericarcinous tissues. Over-expression of NUDCD1 in human CRC tissues was significantly associated with lymph node metastasis, distant metastasis, and advanced stages. The expression of NUDCD1 was higher in all of the CRC cell lines than that in normal colon epithelial mucosal cells. To knockdown NUDCD1 resulted in significant decreases in cell viability and proliferation, decreased protein expression of N-cadherin and increased protein expression of E-cadherin which were biomarkers of EMT, arrested the cell cycle and increased apoptosis via down-regulated cyclin D1, Bcl2, and up-regulated cleaved-caspase3. Furthermore, to knockdown NUDCD1 inactivated IGF1R-ERK1/2 signaling pathway in vitro and in vivo, and suppressed the xenografts of CRC. In conclusion, NUDCD1 promotes the carcinogenesis and metastasis of CRC through inducing EMT and inhibiting apoptosis, which suggests NUDCD1 be a potential biomarker for CRC.

Keywords: Colorectal cancer; EMT; NUDCD1; apoptosis.