骨是小細(xì)胞肺癌（SCLC）轉(zhuǎn)移的最常見的遠(yuǎn)端器官之一,，小細(xì)胞肺癌轉(zhuǎn)移至骨的癌癥患者往往預(yù)后不良,，但到底是什么特異性細(xì)胞基調(diào)控小細(xì)胞肺癌的骨轉(zhuǎn)移，目前還不清楚,。
ZEB1是E-box轉(zhuǎn)錄抑制因子,，早期研究發(fā)現(xiàn)ZEB1對(duì)誘導(dǎo)上皮間質(zhì)轉(zhuǎn)化（EMT）和結(jié)腸癌、乳腺癌和肺癌等腫瘤的轉(zhuǎn)移至關(guān)重要,。然而,，ZEB1和小細(xì)胞肺癌骨轉(zhuǎn)移之間的關(guān)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(shí),，ZEB1高表達(dá)于那些骨轉(zhuǎn)移性非小細(xì)胞肺癌組織和腫瘤細(xì)胞系中,。研究人員使用慢病毒RNA干擾技術(shù)敲除骨轉(zhuǎn)移性非小細(xì)胞肺癌細(xì)胞（SBC-5株）的ZEB1表達(dá),，采用侵襲實(shí)驗(yàn)和酶聯(lián)免疫吸附試驗(yàn)發(fā)現(xiàn)siRNA干擾ZEB1后能抑制腫瘤細(xì)胞的侵襲和遷移能力，降低PTHrP的表達(dá),。,、
此外，siRNA沉默ZEB1表達(dá)后,，能明顯抑制體內(nèi)SBC-5細(xì)胞的骨轉(zhuǎn)移,。SBC-3細(xì)胞過度表達(dá)ZEB1，這說明ZEB1具有促進(jìn)骨轉(zhuǎn)移潛能,，能極大地促進(jìn)腫瘤細(xì)胞的侵襲和遷移能力,，體內(nèi)PTHrP的表達(dá)以及轉(zhuǎn)移至骨的腫瘤細(xì)胞數(shù)量也明顯增加。
同時(shí)研究人員還發(fā)現(xiàn)SBC-3細(xì)胞發(fā)生了EMT過程,，因?yàn)槠渖掀?biāo)記物降低,，間質(zhì)型細(xì)胞標(biāo)記物表達(dá)升高?？傊?，這些結(jié)果證實(shí)ZEB1促進(jìn)小細(xì)胞肺癌細(xì)胞的侵襲能力，能促進(jìn)腫瘤細(xì)胞的骨轉(zhuǎn)移,，其機(jī)制就是部分通過介導(dǎo)EMT途徑,。（生物谷：Bioon.com）
doi:10.1111/j.1349-7006.2012.02347.x
PMC:
PMID:
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.
