K14+/- tumor cell transcriptome. Mus musculus

Conventional models of cancer progression propose that single cells leave the primary tumor, enter the circulation, and seed clonal metastases. However, metastases can contain multiple clones, raising the question: how do polyclonal metastases form? We demonstrate that cancer cells seed distant organs as cohesive clusters, composed of two molecularly distinct subpopulations, whose proportions vary systematically during metastasis. We establish that collective dissemination is a frequent mechanism for metastasis and identify a molecular program in the most invasive, keratin 14+ (K14+) cancer cells, regulating cell-cell adhesion, cell-matrix adhesion, and immune evasion. We demonstrate that this metastatic phenotype is dependent on K14 expression. Understanding the molecular basis of collective dissemination may therefore enable novel prognostics and therapies to improve patient outcomes. This BioProject contains data for our RNA-Seq study of mammary tumor cells sorted by K14 expression.

传统癌症进展模型提出，单个细胞从原发肿瘤脱离，进入血液循环后定植，形成克隆性转移灶。然而转移灶可包含多个克隆，由此引出一个关键问题：多克隆转移灶究竟如何形成？本研究证实，癌细胞以由两种分子特征各异的亚群构成的黏附性细胞簇形式定植远隔器官，且两类亚群的比例在转移进程中呈系统性变化。我们明确了集体播散是肿瘤转移的常见机制，并在侵袭性最强的角蛋白14阳性（keratin 14+, K14+）癌细胞中鉴定出一套调控细胞-细胞黏附、细胞-基质黏附及免疫逃逸的分子程序。我们进一步证实，该转移表型依赖于K14的表达。因此，解析集体播散的分子基础，有望开发新型预后评估工具与治疗策略，进而改善患者临床结局。本生物项目（BioProject）包含我们针对经K14表达分选的乳腺肿瘤细胞开展的RNA测序（RNA-Seq）研究相关数据。