Cancer Sci：ZEB1促进小细胞肺癌骨转移

骨是小细胞肺癌（SCLC）转移的最常见的远端器官之一，小细胞肺癌转移至骨的癌症患者往往预后不良，但到底是什么特异性细胞基调控小细胞肺癌的骨转移，目前还不清楚。

ZEB1是E-box转录抑制因子，早期研究发现ZEB1对诱导上皮间质转化（EMT）和结肠癌、乳腺癌和肺癌等肿瘤的转移至关重要。然而，ZEB1和小细胞肺癌骨转移之间的关系目前还不清楚。

近日发表在Cancer Sci杂志上的一则研究证实，ZEB1高表达于那些骨转移性非小细胞肺癌组织和肿瘤细胞系中。研究人员使用慢病毒RNA干扰技术敲除骨转移性非小细胞肺癌细胞（SBC-5株）的ZEB1表达，采用侵袭实验和酶联免疫吸附试验发现siRNA干扰ZEB1后能抑制肿瘤细胞的侵袭和迁移能力，降低PTHrP的表达。、

此外，siRNA沉默ZEB1表达后，能明显抑制体内SBC-5细胞的骨转移。SBC-3细胞过度表达ZEB1，这说明ZEB1具有促进骨转移潜能，能极大地促进肿瘤细胞的侵袭和迁移能力，体内PTHrP的表达以及转移至骨的肿瘤细胞数量也明显增加。

同时研究人员还发现SBC-3细胞发生了EMT过程，因为其上皮标记物降低，间质型细胞标记物表达升高。总之，这些结果证实ZEB1促进小细胞肺癌细胞的侵袭能力，能促进肿瘤细胞的骨转移，其机制就是部分通过介导EMT途径。

doi:10.1111/j.1349-7006.2012.02347.x
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ZEB1 promotes invasion and bone metastasis of small cell lung cancer in vitro and in vivo.

Liu Y, Zhang N, Wang Y, Xu M, Liu N, Pang X, Cao J, Ma N, Pang H, Liu L, Zhang H.

Bone is one of the most frequent targets of small cell lung cancer (SCLC) metastasis and is closely associated with a poor prognosis, but the specific cellular gene alterations responsible for SCLC with bone metastasis are unclear. ZEB1 as an E-box transcriptional repressor has been suggested that an important inducer of the epithelial-mesenchymal transition (EMT) and a promoter of tumor metastasis in colon, breast, and lung cancers. However, the relationship between ZEB1 and SCLC with bone metastasis is unclear. In this study, ZEB1 was found to be highly expressed in bone-metastatic SCLC tissues and cell lines as compared with those that were non-metastatic (P <0.05). Using a lentivirus RNA interference technique to knockdown ZEB1 expression in bone-metastatic SCLC cells (SBC-5 cell line), we found that ZEB1 siRNA could inhibit the invasive and migratory ability and decrease PTHrP expression, as determined by invasion assays and enzyme-linked immunosorbent assays. Besides, ZEB1 siRNA significantly inhibited the bone metastasis of SBC-5 cells in vivo. Furthermore, overexpression of ZEB1 in SBC-3 cells, which demonstrate promoted bone-metastatic potential, dramatically promoted their invasive and migratory ability and PTHrP expression as well as increased the number and sites of bone metastases in vivo compare to the control group. We also found that SBC-3 cells underwent EMT, as indicated by decreased epithelial markers and increased mesenchymal markers expression. Taken together, these results indicated that ZEB1 promoted the invasive ability and bone metastasis of SCLC cells, and that this was partially mediated via the EMT pathway.