Snai1 and Snai2 collaborate on tumor growth and metastasis properties of mouse skin carcinoma cell lines
Snai1 and Snai2 collaborate on tumor growth and metastasis properties of mouse skin carcinoma cell lines
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DOI：
10.1038/onc.2008.118
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发表时间：
2008-08-01
期刊：
影响因子：
8
通讯作者：
Cano, A.
中科院分区：
文献类型：
--
作者：
Olmeda, D.;Montes, A.;Cano, A.
Snai1(Snail)和SNAI2(Slug)是Snail家族因子的两个主要成员，是上皮-间充质转化的重要介质，参与肿瘤的发展。我们最近报道了SnAI1在肿瘤的生长、侵袭和转移中起重要作用，但SNAI2在肿瘤发生中的作用尚不清楚。为了解决这个问题，我们在两个独立的小鼠皮肤癌细胞系(HaCa4和CarB)中通过稳定的RNA干扰使SNAI2和/或Snai1沉默。我们证明，当注射到裸鼠体内时，SNAI2基因敲除有较温和的效果，但与Snai1沉默协同作用，降低了任一种癌细胞系的肿瘤生长潜力。重要的是，Snai1或SNAI2沉默显著影响鳞癌HaCa4细胞的转移能力，导致肝和肺远处转移的显著减少。然而，只有Snai1基因敲除具有有效的侵袭性作用，并完全消除肿瘤细胞向脾内的扩散。这些结果表明，Snai1和SNAI2在原发肿瘤生长中协同作用，并特异性地促进HaCa4细胞的部位特异性转移。这些数据还表明，Snai1是局部侵袭的主要调节因子，支持这两个因素在转移过程中的分级参与。
Snai1 (Snail) and Snai2 (Slug), the two main members of Snail family factors, are important mediators of epithelial-mesenchymal transitions and involved in tumor progression. We recently reported that Snai1 plays a major role in tumor growth, invasion and metastasis, but the contribution of Snai2 to tumorigenesis is not yet well understood. To approach this question we have silenced Snai2 and/or Snai1 by stable RNA interference in two independent mouse skin carcinoma (HaCa4 and CarB) cell lines. We demonstrate that Snai2 knockdown has a milder effect, but collaborates with Snai1 silencing in reduction of tumor growth potential of either carcinoma cell line when injected into nude mice. Importantly, Snai1 or Snai2 silencing dramatically influences the metastatic ability of squamous carcinoma HaCa4 cells, inducing a strong reduction in liver and lung distant metastasis. However, only Snai1 knockdown has an effective action on invasiveness and fully abolishes tumor cell dissemination into the spleen. These results demonstrate that Snai1 and Snai2 collaborate on primary tumor growth and specifically contribute to site-specific metastasis of HaCa4 cells. These data also indicate that Snai1 is the major regulator of local invasion, supporting a hierarchical participation of both factors in the metastatic process.