Li Qinghua, Wang Yanlan, Lai Yuexing, Xu Ping, Yang Zhiwen
Songjiang Hospital Affiliated Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Songjiang Hospital Affiliated to Nanjing Medical University, Nanjing, China.
PLoS One. 2017 Aug 10;12(8):e0182588. doi: 10.1371/journal.pone.0182588. eCollection 2017.
Alpha B-crystallin (HspB5) is abnormally expressed in tumor tissues and portends a poor prognosis in cancer patients. However, the role of HspB5 in colorectal cancer (CRC) is still unclear. Seventy CRC patients and 40 healthy volunteers were sampled from August 2012 to March 2015 in order to determine the clinical significance of HspB5. In vitro cellular studies were used to validate its molecular mechanisms in CRC. Our clinical data indicated that HspB5 was up-regulated, and had a positive association with TNM stage CRC patients. The expression level of HspB5 in CRC patients was closely correlated with MMP7 and E-cadherin, two core epithelial-mesenchymal transition (EMT) gene products. The in vitro studies revealed that high HspB5 expression could prompt tumor cell proliferation and invasion, as well as EMT. Gene-microarray analysis suggested three significant signaling pathways (PI3K, p38 and ERK) were involved in HspB5-induced EMT. Signal transduction pathway inhibitors and HspB5 gene knockdown models suggested that HspB5 promotes CRC tumorigenesis and EMT progression through ERK signaling pathways. In summary, HspB5 maybe trigger the EMT in CRC by activating the ERK signaling pathway. It is a potential tumor biomarker for CRC diagnosis and prognosis.
αB-晶状体蛋白（热休克蛋白B5）在肿瘤组织中异常表达，提示癌症患者预后不良。然而，热休克蛋白B5在结直肠癌（CRC）中的作用仍不清楚。2012年8月至2015年3月，对70例CRC患者和40名健康志愿者进行采样，以确定热休克蛋白B5的临床意义。采用体外细胞研究来验证其在CRC中的分子机制。我们的临床数据表明，热休克蛋白B5上调，且与CRC患者的TNM分期呈正相关。CRC患者中热休克蛋白B5的表达水平与两种核心上皮-间质转化（EMT）基因产物MMP7和E-钙黏蛋白密切相关。体外研究表明，热休克蛋白B5高表达可促进肿瘤细胞增殖、侵袭以及EMT。基因芯片分析提示PI3K、p38和ERK三条重要信号通路参与热休克蛋白B5诱导的EMT。信号转导通路抑制剂和热休克蛋白B5基因敲低模型提示，热休克蛋白B5通过ERK信号通路促进CRC肿瘤发生和EMT进展。总之，热休克蛋白B5可能通过激活ERK信号通路触发CRC中的EMT。它是CRC诊断和预后的潜在肿瘤生物标志物。
