IL-7/IL-7 receptor axis stimulates prostate cancer cell invasion and migration via AKT/NF-κB pathway.
IL-7, acting via IL-7 receptor (IL-7R), plays an important role in tumor progression. Elevated IL-7 expression has been reported to be observed in prostate cancer tissues and closely associated with poor prognosis. However, the biological functions of IL-7 and its receptor in prostate cancer cell invasiveness remain unclear. In our study, we found that the expressions of IL-7 and IL-7R were both upregulated in prostate cancer cells. IL-7 dose-dependently promoted the invasion and migration of prostate cancer cells, whereas knockdown of IL-7R attenuated the effect of IL-7. Further, IL-7/IL-7R axis induced the activation of AKT and NF-κB, whereas blocking of AKT suppressed IL-7-mediated NF-κB activity. Moreover, IL-7/IL-7R axis increased MMP-3 and MMP-7 expression of prostate cancer cells, whereas inhibition of NF-κB as well as MMPs activity suppressed IL-7-mediated cell invasion and migration. Together, these data identify IL-7/IL-7R axis to be involved in prostate cancer cell invasion and migration, probably via activating AKT/NF-κB pathway and upregulating MMP-3 and MMP-7 expression. Therefore, blocking IL-7/IL-7R axis may provide a potential therapeutic strategy to treat prostate cancer.
Department of Urology, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, PR China.
Hu
H
Qu
Department of Urology, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, PR China.
Zihao
Z
Zou
Department of Urology, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, PR China.
Zhaojun
Z
Pan
Department of Urology, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, PR China.
Tianwei
T
Zhang
Department of Urology, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, PR China.
Nan
N
Deng
Department of Urology, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, PR China.
Guoxi
G
Chen
Department of Urology, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, PR China. Electronic address: zsslymnwk@163.com.
Zhongyang
Z
Wang
D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D006801:Humans; D015851:Interleukin-7 / Q000378:metabolism*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D020395:Receptors, Interleukin-7 / Q000378:metabolism*; D015398:Signal Transduction
D015851:Interleukin-7; D016328:NF-kappa B; D020395:Receptors, Interleukin-7; D051057:Proto-Oncogene Proteins c-akt; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7
AKT; IL-7; IL-7R; Invasion; NF-κB; Prostate cancer