Work

Cell lineage tracing links ERα loss in Erbb2-positive breast cancers to the arising of a highly aggressive breast cancer subtype

Year: 2021

Type: article

Abstract: Significance HER2 + breast cancers (BrCs) are heterogeneous, but they are treated as a single type. Using a mouse model with Erbb2 (the rodent homolog of HER2)-induced BrC and cell lineage-tracing capacity, we found that ERα + Erbb2 + cancer cells proliferate slowly and are nonmetastatic but then progressively lose ERα expression to become fast proliferating and highly metastatic ERα − Erbb2 + cancer cells. ERα − Erbb2 + cancer cells with an ERα − origin proliferate fast, but they metastasize weakly. These findings suggest: 1) ERα expression should be preserved in ERα + HER2 + BrCs to restrict growth and metastasis; 2) ERα − HER2 + BrCs contain a highly metastatic subtype with an ERα + origin and a weakly metastatic subtype with an ERα − origin, indicating a future need to identify and differentially treat these two subtypes.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.2100673118