骨是小細胞肺癌（SCLC）轉移的最常見的遠端器官之一,，小細胞肺癌轉移至骨的癌癥患者往往預后不良,，但到底是什么特異性細胞基調控小細胞肺癌的骨轉移，目前還不清楚,。
ZEB1是E-box轉錄抑制因子，早期研究發(fā)現(xiàn)ZEB1對誘導上皮間質轉化（EMT）和結腸癌,、乳腺癌和肺癌等腫瘤的轉移至關重要,。然而，ZEB1和小細胞肺癌骨轉移之間的關系目前還不清楚,。
近日發(fā)表在Cancer Sci雜志上的一則研究證實,，ZEB1高表達于那些骨轉移性非小細胞肺癌組織和腫瘤細胞系中。研究人員使用慢病毒RNA干擾技術敲除骨轉移性非小細胞肺癌細胞（SBC-5株）的ZEB1表達,，采用侵襲實驗和酶聯(lián)免疫吸附試驗發(fā)現(xiàn)siRNA干擾ZEB1后能抑制腫瘤細胞的侵襲和遷移能力,，降低PTHrP的表達。、
此外,，siRNA沉默ZEB1表達后,，能明顯抑制體內SBC-5細胞的骨轉移。SBC-3細胞過度表達ZEB1,，這說明ZEB1具有促進骨轉移潛能,，能極大地促進腫瘤細胞的侵襲和遷移能力，體內PTHrP的表達以及轉移至骨的腫瘤細胞數(shù)量也明顯增加,。
同時研究人員還發(fā)現(xiàn)SBC-3細胞發(fā)生了EMT過程,，因為其上皮標記物降低，間質型細胞標記物表達升高,?？傊@些結果證實ZEB1促進小細胞肺癌細胞的侵襲能力,，能促進腫瘤細胞的骨轉移,，其機制就是部分通過介導EMT途徑。（生物谷：Bioon.com）
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.
