p Verdinexor, a Selective Inhibitor of Nuclear Exportin 1, Inhibits the Proliferation and Migration of Esophageal Cancer via XPO1/c-Myc/FOSL1 Axis

Ou, Ling1,2,7; Wang, Xinyou3; Cheng, Shumin1,2; Zhang, Min1,2; Cui, Ruiqin1,2; Hu, Chunxia1,2; Liu, Shiyi1,2; Tang, Qian2,4,5; Peng, Yuying2,4,5; Chai, Ruihuan6; Xie, Shouxia2,4; Wang, Shaoxiang6; Huang, Wei1,2; Wang, Xiao2,4,5

2022

10.7150/ijbs.66612

International Journal of Biological Sciences   影响因子和分区

1449-2288

Esophageal carcinoma (EC) ranks sixth among cancers in mortality worldwide and effective drugs to reduce EC incidence and mortality are lacking. To explore potential anti-esophageal cancer drugs, we conducted drug screening and discovered that verdinexor, a selective inhibitor of nuclear exportin 1 (XPO1/CRM1), has anti-esophageal cancer effects both in vivo and in vitro. However, the mechanism and role of verdinexor in esophageal cancer remain unknown. In the present study, we observed that verdinexor inhibited the proliferation and migration of EC cells in vitro and suppressed tumor growth in vivo. Additionally, we found that verdinexor induced cleavage of PARP and downregulated XPO1, c-Myc, and FOSL1 expression. RNA-sequence analysis and protein-protein interaction (PPI) analysis revealed that verdinexor regulated the XPO1/c-Myc/FOSL1 axis. The results of immunoprecipitation and proximity ligation assays confirmed that verdinexor disrupted the interaction between XPO1 and c-Myc. Overexpression of c-Myc rescued the inhibition of cell proliferation and cell migration caused by verdinexor. Overexpressed FOSL1 restored the inhibited migration by verdinexor. Taken together, verdinexor inhibited cell proliferation and migration of esophageal cancer via XPO1/c-Myc/FOSL1 axis. Our findings provide a new option for the development of anti-esophageal cancer drugs.

Verdinexor XPO1 esophageal cancer c-Myc FOSL1

SCI

英语

通讯

National Natural Science Foundation of China[82073937,82173859] ; Guangdong Basic and Applied Basic Research Foundation[2020B1515120066] ; Shenzhen Key Medical Discipline Construction Fund[SZXK059] ; Shenzhen Key Laboratory of Prevention and Treatment of Severe Infections[ZDSYS20200811142804014] ; Shenzhen Science and Technology Project["JCYJ20180228175059744","JCYJ20180305163929948","GJHZ20200731095200003","JCYJ20210324093602007"] ; SZU Medical Young Scientists Program[71201-000001]

Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics

Biochemistry & Molecular Biology ; Biology

WOS:000741522700006

IVYSPRING INT PUBL

Web of Science

1.Jinan Univ, Clin Med Coll 2, Bacteriol & Antibacterial Resistance Surveillance, Shenzhen Peoples Hosp,Shenzhen Inst Resp Dis, Shenzhen 518020, Guangdong, Peoples R China
2.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518020, Guangdong, Peoples R China
3.Sun Yat Sen Univ, Affiliated Hosp 6, Dist Gastrointestinal Surg 1, Guangzhou, Guangdong, Peoples R China
4.Jinan Univ, Clin Med Coll 2, Shenzhen Peoples Hosp, Dept Pharm, Shenzhen 518020, Guangdong, Peoples R China
5.Jinan Univ, Sch Pharm, Guangzhou 510630, Guangdong, Peoples R China
6.Shenzhen Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Shenzhen 518000, Guangdong, Peoples R China
7.Sun Yat Sen Univ, Sch Pharmaceut Sci Shenzhen, Shenzhen 518107, Guangdong, Peoples R China

Ou, Ling,Wang, Xinyou,Cheng, Shumin,et al. p Verdinexor, a Selective Inhibitor of Nuclear Exportin 1, Inhibits the Proliferation and Migration of Esophageal Cancer via XPO1/c-Myc/FOSL1 Axis[J]. International Journal of Biological Sciences,2022,18(1).

Ou, Ling.,Wang, Xinyou.,Cheng, Shumin.,Zhang, Min.,Cui, Ruiqin.,...&Wang, Xiao.(2022).p Verdinexor, a Selective Inhibitor of Nuclear Exportin 1, Inhibits the Proliferation and Migration of Esophageal Cancer via XPO1/c-Myc/FOSL1 Axis.International Journal of Biological Sciences,18(1).

Ou, Ling,et al."p Verdinexor, a Selective Inhibitor of Nuclear Exportin 1, Inhibits the Proliferation and Migration of Esophageal Cancer via XPO1/c-Myc/FOSL1 Axis".International Journal of Biological Sciences 18.1(2022).