SPOCK1 is a novel transforming growth factor-β target gene that regulates lung cancer cell epithelial-mesenchymal transition
SPOCK1 is a novel transforming growth factor-β target gene that regulates lung cancer cell epithelial-mesenchymal transition
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DOI：
10.1016/j.bbrc.2013.10.024
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发表时间：
2013-11-01
影响因子：
3.1
通讯作者：
Song, Yong
中科院分区：
文献类型：
--
作者：
Miao, Liyun;Wang, Yongsheng;Song, Yong
肺癌是世界范围内与癌症相关的死亡的主要原因，预后仍然很差，5年生存率约为15%。转移是癌症致死的主要原因。最近的研究表明，上皮向间充质转化(EMT)在癌细胞的早期转移过程中起着关键作用。在此，我们发现SPARC/Osteonectin，Cwcv和Kazal-like结构域蛋白多糖1(SPOCK1)是一个新的调控肺癌细胞EMT的转化生长因子-β1(TGF-β1)靶基因。转化生长因子-β已被报道为EMT的主要诱导物。我们观察到SPOCK1在肺癌肿瘤组织中的表达明显高于匹配的正常肺组织。此外，SPOCK1在转移癌组织中的表达也显著高于非转移瘤组织。无瘤生存期短的患者SPOCK1mRNA水平升高，提示SPOCK1在肺癌进展和转移中可能起作用。用核酸内切酶制备的小干扰RNA(EsiRNA)沉默肺细胞中SPOCK1的表达可在体外抑制肺癌细胞的生长、克隆形成和侵袭。有趣的是，SPOCK1在上皮性肺癌细胞中的异位表达诱导了EMT，间质标记物Vimentin的表达增加，上皮标记物E-cadherin的表达降低。我们还发现，在转化生长因子-β作用下，SPOCK1的表达增加，表明SPOCK1是转化生长因子-β的一个新的下游靶点。综上所述，我们的研究表明，SPOCK1是一种新的肺癌转移相关生物标志物，可能成为肺癌诊断和治疗的新靶点。(C)2013 Elsevier Inc.保留所有权利。
Lung cancer is the leading cause of cancer related death worldwide and the prognosis is still poor with 5-year survival of approximately 15%. Metastasis is the leading cause of death by cancer. Recent researches have demonstrated that epithelial-to-mesenchymal transition (EMT) plays a key role in the early process of metastasis of cancer cells. Here, we identified that SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 1 (SPOCK1) is a novel transforming growth factor-beta 1 (TGF-beta) target gene that regulates lung cancer cell EMT. TGF-beta has been reported as a major inductor of EMT. We observed that the expression of SPOCK1 in lung cancer tumor tissues is significantly higher than matched normal lung tissues. Moreover, the expression of SPOCK1 was also significantly higher in metastasis tumor tissues than non-metastasis tumor tissues. Levels of SPOCK1 mRNA were increased among patients with shorter disease-free survival times, indicating the potential role of SPOCK1 in lung cancer progression and metastasis. Silencing SPOCK1 expression with endoribonuclease-prepared small interfering RNA (esiRNA) in lung cells inhibits lung cancer cell growth, colony formation and invasion in vitro. Interestingly, ectopic expression of SPOCK1 in epithelial lung cancer cells induced EMT with increased expression of the mesenchymal marker Vimentin and decreased expression of epithelial marker E-cadherin. We also found that the expression of SPOCK1 was increased under treatment of TGF-beta, indicating that SPOCK1 is a novel downstream target of TGF-beta. Taken together, our study showed that SPOCK1 is a novel metastasis related biomarker in lung cancer and may be new diagnostic and therapeutic target for lung cancer. (C) 2013 Elsevier Inc. All rights reserved.