Κυριακή 8 Νοεμβρίου 2020

Single-cell transcriptomic heterogeneity in invasive ductal and lobular breast cancer cells

alwin shared this article with you from Inoreader
Invasive lobular breast carcinoma (ILC), one of the major breast cancer histological subtypes, exhibits unique features compared to the well-studied ductal cancer subtype (IDC). The pathognomonic feature of ILC is loss of E-cadherin, mainly caused by inactivating mutations, but the contribution of this genetic alteration to ILC-specific molecular characteristics remains largely understudied. To profile these features transcriptionally, we conducted single-cell-RNA-sequencing on a panel of IDC and ILC cell lines, and an IDC cell line (T47D) with CRISPR-Cas9-mediated E-cadherin knock out (KO). Inspection of intra-cell line heterogeneity illustrated genetically and transcriptionally distinct subpopulations in multiple cell lines and highlighted rare populations of MCF7 cells highly expressing an apoptosis-related signature, positively correlated with a pre-adaptation signature to estrogen deprivation. Investigation of E-cadherin KO-induced alterations showed transcriptomic membran ous systems remodeling, elevated resemblance to ILCs in regulon activation, and increased sensitivity to IFN-γ mediated growth inhibition via activation of IRF1. This study reveals single cell transcriptional heterogeneity in breast cancer cell lines and provides a resource to identify drivers of cancer progression and drug resistance.
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