Yao Juntao, Yao Xuan, Tian Tao, Fu Xiao, Wang Wenjuan, Li Suoni, Shi Tingting, Suo Aili, Ruan Zhiping, Guo Hui, Nan Kejun, Huo Xiongwei
Oncol Res. 2017 Mar 13;25(3):305-316. doi: 10.3727/096504016X14734149559061.
ABCB5 belongs to the ATP-binding cassette (ABC) superfamily, which is recognized for playing a role in the failure of chemotherapy. ABCB5 has also been found to be overexpressed at the transcriptional level in a number of cancer subtypes, including breast cancer. However, the exact mechanism ABCB5 uses on cancer cell metastasis is still unclear. In the present study, we demonstrate that ABCB5 expression was increased in metastatic tissues when compared with nonmetastatic tissues. ABCB5 can significantly enhance metastasis and epithelial-mesenchymal transition (EMT), while knockdown of ABCB5 inhibited these processes. Microarray analysis indicated that ZEB1 may function as a downstream factor of ABCB5. Furthermore, the expression of ZEB1 in tissues is positively relevant to ABCB5 in breast cancer. Knocking down ZEB1 inhibits ABCB5 ectopic expression-induced migration and invasion, as well as EMT. Taken together, these results helped to realize the oncogene functions of ABCB5 in breast cancer cells and provided a new direction in treating breast cancer.
ABCB5属于ATP结合盒(ABC)超家族,该家族因在化疗失败中起作用而被人们所熟知。ABCB5也已被发现在包括乳腺癌在内的多种癌症亚型中在转录水平上过度表达。然而,ABCB5作用于癌细胞转移的确切机制仍不清楚。在本研究中,我们证明与非转移组织相比,ABCB5在转移组织中的表达增加。ABCB5可显著增强转移和上皮-间质转化(EMT),而敲低ABCB5则抑制这些过程。基因芯片分析表明,ZEB1可能作为ABCB5的下游因子发挥作用。此外,在乳腺癌组织中ZEB1的表达与ABCB5呈正相关。敲低ZEB1可抑制ABCB5异位表达诱导的迁移、侵袭以及EMT。综上所述,这些结果有助于认识ABCB5在乳腺癌细胞中的致癌基因功能,并为治疗乳腺癌提供了新的方向。