Stepping on the GAS: a brake pedal for melanoma metastasis?
Stepping on the GAS: a brake pedal for melanoma metastasis?
复制标题
踩下GAS：黑色素瘤转移的刹车踏板？
DOI：
10.1111/j.1755-148x.2008.00533.x
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发表时间：
2009
影响因子：
4.3
通讯作者：
Garraway,LeviA
中科院分区：
文献类型：
--
作者：
Linja,Marika;Garraway,LeviA
转移性黑色素瘤是众所周知的难治性的大多数药物治疗，因此，阐述黑色素瘤转移的生物学基础可能会加速新的治疗方法，降低这种恶性肿瘤的死亡率的发展。尽管近年来我们对其分子基础的理解取得了相当大的进展，但特异性调节黑色素瘤转移过程的因素仍不完全清楚。为了获得转移潜力，癌细胞必须学会侵入其周围基质，通过血流或动脉存活，并成功地定植在继发部位。在这样做时，它们产生各种转移促进基因，同时下调抑制该过程的称为转移抑制基因的其他基因（由Rinker-Schaeffer等人综述，2006年）。然而，很少有可扩展的实验系统已经开发到查询的关键调控组件，这多步骤的现象在vitrial.The出现的RNAi为基础的方法，在哺乳动物系统中的定向基因沉默，与全基因组的“短发夹”RNAi（shRNA）库的可用性提供了前所未有的途径，系统的讯问癌症相关的表型。近年来，使用逆转录病毒或慢病毒载体稳定引入和筛选汇集的shRNA文库已经产生了许多与几种肿瘤类型相关的新生物学见解。通过采用基于微阵列的“半发夹”DNA条形码来鉴定在选择后已经富集或耗尽的shRNA，合并的RNAi筛选提供了越来越容易获得的手段，以无偏的方式和在基因组规模上询问肿瘤过程（Schlabach et al. 2008年）。
Metastatic melanoma is notoriously refractory to most medical therapies; therefore, elaborating the biological basis of metastasis in melanoma may speed the development of novel therapeutic approaches that reduce mortality from this malignancy. Although recent years have witnessed considerable advances in our understanding of its molecular underpinnings, factors that specifically modulate the metastatic process in melanoma remain incompletely understood. To acquire metastatic potential, cancer cells must learn to invade into their surrounding matrix, survive passage through the bloodstream or lymphatics, and successfully colonize secondary sites. In doing so, they enact various metastasis-promoting genes while down-modulating other genes, termed metastasis suppressor genes, that inhibit this process (reviewed by Rinker-Schaeffer et al., 2006). However, few scalable experimental systems have been developed to query the key regulatory components of this multi-step phenomenon in vitro.The advent of RNAi-based methodologies for directed gene silencing in mammalian systems, together with the availability of genome-wide “short hairpin” RNAi (shRNA) libraries have provided unprecedented avenues for systematic interrogation of cancerassociated phenotypes. In recent years, the stable introduction and screening of pooled shRNA libraries using retroviral or lentiviral vectors has yielded numerous new biological insights relevant to several tumor types. By employing microarray-based “half hairpin” DNA barcodes to identify shRNAs that have become enriched or depleted following selections, pooled RNAi screens offer an increasingly accessible means to interrogate tumor processes in an unbiased fashion and at a genome scale (Schlabach et al., 2008).