Single-cell transcriptomics reveals involution mimicry during the specification of the basal breast cancer subtype
Single-cell transcriptomics reveals involution mimicry during the specification of the basal breast cancer subtype
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DOI：
10.1016/j.celrep.2021.108945
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发表时间：
2021-04-13
期刊：
影响因子：
8.8
通讯作者：
Gallego-Ortega, David
中科院分区：
文献类型：
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作者：
Valdes-Mora, Fatima;Salomon, Robert;Gallego-Ortega, David
基底部乳腺癌与年轻、早期复发和高死亡率相关。在这里，我们使用无偏的基于液滴的单细胞RNA测序（RNA-seq）来阐明在MMTV-PyMT（小鼠乳腺肿瘤病毒-多瘤中间肿瘤-抗原）乳腺肿瘤模型中从管腔祖细胞群体中指定基底乳腺癌亚型期间肿瘤进展的细胞基础。我们发现基底样癌细胞类似于妊娠时指定的肺泡谱系，并包括获得异常的哺乳后发育退化程序，从而引发肿瘤微环境的重塑和转移性播散。这种退化模拟的特征在于高度相互作用的多细胞网络，退化癌症相关的成纤维细胞在细胞外基质重塑和免疫抑制中发挥关键作用。我们的研究结果可以部分解释与分娩相关的乳腺癌风险增加和预后不良。
Basal breast cancer is associated with younger age, early relapse, and a high mortality rate. Here, we use unbiased droplet-based single-cell RNA sequencing (RNA-seq) to elucidate the cellular basis of tumor progression during the specification of the basal breast cancer subtype from the luminal progenitor population in the MMTV-PyMT (mousemammary tumor virus-polyoma middle tumor-antigen) mammary tumor model. We find that basal-like cancer cells resemble the alveolar lineage that is specified upon pregnancy and encompass the acquisition of an aberrant post-lactation developmental program of involution that triggers remodeling of the tumor microenvironment and metastatic dissemination. This involution mimicry is characterized by a highly interactive multicellular network, with involution cancer-associated fibroblasts playing a pivotal role in extracellular matrix remodeling and immunosuppression. Our results may partially explain the increased risk and poor prognosis of breast cancer associated with childbirth.