Knockdown of Notch1 inhibits nasopharyngeal carcinoma cell growth and metastasis via downregulation of CCL2, CXCL16, and uPA

Guo, Huajiao1; Wang, Fuhao2; Diao, Yuwen2; Zhang, Zhe3; Chen, Qiuyan4; Qian, Chao-Nan4; Keller, Evan T.5; Zhang, Jian2,6; Lu, Yi2,6

2019-07-03

10.1002/mc.23082

MOLECULAR CARCINOGENESIS   影响因子和分区

0899-1987

1098-2744

Notch pathway is a highly conserved cell signaling system that plays very important roles in controlling multiple cell differentiation processes during embryonic and adult life. Multiple lines of evidence support the oncogenic role of Notch signaling in several human solid cancers; however, the pleiotropic effects and molecular mechanisms of Notch signaling inhibition on nasopharyngeal carcinoma (NPC) remain unclear. In this study, we evaluated Notch1 expression in NPC cell lines (CNE1, CNE2, SUNE1, HONE1, and HK1) by real-time quantitative PCR and Western blot analysis, and we found that CNE1 and CNE2 cells expressed a higher level of Notch1 compared with HONE1, SUNE1, and HK1 cells. Then Notch1 expression was specifically knocked down in CNE1 and CNE2 cells by Notch1 short hairpin RNA (shRNA). In Notch1 knockdown cells, cell proliferation, migration, and invasion were significantly inhibited. The epithelial-mesenchymal transition of tumor cells was reversed in Notch1-shRNA-transfected cells, accompanied by epithelioid-like morphology changes, increased protein levels of E-cadherin, and decreased expression of vimentin. In addition, knockdown of Notch1 markedly inhibited the expression of urokinase plasminogen activator (uPA) and its receptor uPAR, and chemokines C-C motif chemokine ligand 2 and C-X-C motif chemokine ligand 16, indicating that these factors are downstream targets of Notch1. Furthermore, deleting uPA expression had similar effects as Notch1. Finally, knockdown of Notch1 significantly diminished CNE1 cell growth in a murine model concomitant with inhibition of cell proliferation and induction of apoptosis. These results suggest that Notch1 may become a novel therapeutic target for the clinical treatment of NPC.

CCL2 EMT nasopharyngeal carcinoma Notch1 uPA

SCI

英语

通讯

Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research[2017B030301018]

Biochemistry & Molecular Biology ; Oncology

Biochemistry & Molecular Biology ; Oncology

WOS:000474029200001

WILEY

CLINICAL MEDICINE

Web of Science

1.Beihai Peoples Hosp, Dept Oncol, Beihai, Guangxi, Peoples R China
2.Southern Univ Sci & Technol, Sch Med, 1088 Xue Yuan Blvd, Shenzhen 518055, Guangdong, Peoples R China
3.Guangxi Med Univ, Dept Otolaryngol, Affiliated Hosp 1, Nanning, Guangxi, Peoples R China
4.Sun Yat Sen Univ, Canc Ctr, Dept Nasopharyngeal Carcinoma, Guangzhou, Guangdong, Peoples R China
5.Univ Michigan, Sch Med, Dept Urol & Pathol, Ann Arbor, MI USA
6.Guangdong Prov Key Lab Cell Microenvironm & Dis R, Shenzhen, Guangdong, Peoples R China

Guo, Huajiao,Wang, Fuhao,Diao, Yuwen,et al. Knockdown of Notch1 inhibits nasopharyngeal carcinoma cell growth and metastasis via downregulation of CCL2, CXCL16, and uPA[J]. MOLECULAR CARCINOGENESIS,2019,58(10):1886-1896.

Guo, Huajiao.,Wang, Fuhao.,Diao, Yuwen.,Zhang, Zhe.,Chen, Qiuyan.,...&Lu, Yi.(2019).Knockdown of Notch1 inhibits nasopharyngeal carcinoma cell growth and metastasis via downregulation of CCL2, CXCL16, and uPA.MOLECULAR CARCINOGENESIS,58(10),1886-1896.

Guo, Huajiao,et al."Knockdown of Notch1 inhibits nasopharyngeal carcinoma cell growth and metastasis via downregulation of CCL2, CXCL16, and uPA".MOLECULAR CARCINOGENESIS 58.10(2019):1886-1896.