Collective invasion in breast cancer requires a conserved basal epithelial program.
Collective invasion in breast cancer requires a conserved basal epithelial program.
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DOI：
10.1016/j.cell.2013.11.029
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发表时间：
2013-12-19
期刊：
影响因子：
64.5
通讯作者：
Ewald AJ
中科院分区：
文献类型：
--
作者：
Cheung KJ;Gabrielson E;Werb Z;Ewald AJ
癌通常作为一个有凝聚力的多细胞单元进行侵袭，这一过程被称为集体侵袭。目前尚不清楚癌细胞的不同亚群如何对这一过程有贡献。我们开发了三维（3D）类器官检测方法，以识别原发性乳腺肿瘤中最具侵袭性的癌细胞。集体侵袭是由特定的癌细胞引领的，这些癌细胞由其基底上皮基因的表达所定义，比如细胞角蛋白 - 14（K14）和p63。此外，K14 +细胞在主要的人类乳腺癌亚型中引领集体侵袭。重要的是，观察到管腔癌细胞在诱导基底上皮基因后表型上转变为侵袭性的引领细胞。尽管管腔肿瘤内只有少数细胞表达基底上皮基因，但敲低K14或p63中的任何一个都足以阻断集体侵袭。我们的数据显示，上皮亚群之间的异型相互作用对集体侵袭至关重要。我们认为，靶向基底侵袭程序可能会限制转移进展。
Carcinomas typically invade as a cohesive multicellular unit, a process termed collective invasion. It remains unclear how different subpopulations of cancer cells contribute to this process. We developed three-dimensional (3D) organoid assays to identify the most invasive cancer cells in primary breast tumors. Collective invasion was led by specialized cancer cells that were defined by their expression of basal epithelial genes, such as cytokeratin-14 (K14) and p63. Furthermore, K14+ cells led collective invasion in the major human breast cancer subtypes. Importantly, luminal cancer cells were observed to convert phenotypically to invasive leaders following induction of basal epithelial genes. Although only a minority of cells within luminal tumors expressed basal epithelial genes, knockdown of either K14 or p63 was sufficient to block collective invasion. Our data reveal that heterotypic interactions between epithelial subpopulations are critical to collective invasion. We suggest that targeting the basal invasive program could limit metastatic progression.
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