Shen Hai-bo, Gu Zheng-qin, Jian Kang, Qi Juan
Department of Urology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
Tumour Biol. 2013 Jun;34(3):1839-45. doi: 10.1007/s13277-013-0725-z. Epub 2013 Mar 23.
CXCL12/CXCR4 signaling plays important roles in tumor cell metastasis in many types of cancers, and CXCR4 is the key regulator of cell motility in bladder cancer. Emerging evidence suggests that transcription-3 (Stat3) activation is associated with bladder cancer cell growth and survival, while the relationship between CXCL12/CXCR4 signal and Stat3 activation remains unclear. In this study, expression analysis of bladder cancer and adjacent normal tissues showed that higher CXCR4 expression was associated with Stat3 phosphorylation. CXCR4 knockdown in bladder cancer T24 cells impaired CXCL12-induced cell invasion and Stat3 activation. Furthermore, blocking Stat3 activity with the chemical inhibitor Stattic inhibited CXCL12-triggered Stat3 phosphorylation and cell invasion in T24 cells, suggesting that Stat3 activation is required for CXCL12 function in the mobility of bladder cancer. Taken together, CXCR4 is necessary for CXCL12 signal transduction in bladder cancer, and CXCL12/CXCR4 promotes invasion of bladder cancer cells through activation of Stat3 transcriptional activity.
CXCL12/CXCR4信号通路在多种癌症的肿瘤细胞转移中发挥重要作用，且CXCR4是膀胱癌中细胞运动的关键调节因子。新出现的证据表明，信号转导与转录激活因子3（Stat3）的激活与膀胱癌细胞的生长和存活相关，而CXCL12/CXCR4信号与Stat3激活之间的关系仍不清楚。在本研究中，对膀胱癌组织和相邻正常组织的表达分析表明，较高的CXCR4表达与Stat3磷酸化相关。在膀胱癌T24细胞中敲低CXCR4会损害CXCL12诱导的细胞侵袭和Stat3激活。此外，用化学抑制剂Stattic阻断Stat3活性可抑制T24细胞中CXCL12触发的Stat3磷酸化和细胞侵袭，这表明Stat3激活是CXCL12在膀胱癌细胞迁移中发挥功能所必需的。综上所述，CXCR4是CXCL12在膀胱癌中信号转导所必需的，且CXCL12/CXCR4通过激活Stat3转录活性促进膀胱癌细胞的侵袭。
