Identification of a novel ER-NFĸB-driven stem-like cell population associated with relapse of ER+ breast tumors.

Background: Up to 40% of patients with estrogen receptor-positive (ER+) breast cancer experience relapse. This can be attributed to breast cancer stem cells (BCSCs), which are known to be involved in therapy resistance, relapse, and metastasis. Therefore, there is an urgent need to identify genes/pathways that drive stem-like cell properties in ER+ breast tumors.

Estrogen Receptor-Regulated Gene Signatures in Invasive Breast Cancer Cells and Aggressive Breast Tumors.

Most metastatic breast cancers arise from estrogen receptor α (ER)-positive disease, and yet the role of ER in promoting metastasis is unclear. Here, we used an ER+ breast cancer cell line that is highly invasive in an ER- and IKKβ-dependent manner. We defined two ER-regulated gene signatures that are specifically regulated in the subpopulations of invasive cells.

Selective pressure of endocrine therapy activates the integrated stress response through NFκB signaling in a subpopulation of ER positive breast cancer cells.

Background: While estrogen receptor (ER) positive breast tumors generally respond well to endocrine therapy (ET), up to 40% of patients will experience relapse, either while on endocrine therapy or after ET is completed. We previously demonstrated that the selective pressure of tamoxifen activates the NFκB pathway in ER + patient tumors, breast cancer cell lines, and breast cancer xenograft tumors, and that this activation allows for survival of a subpopulation of NFκB + cells that contribute to cell regrowth and tumor relapse after ET withdrawal. However, the mechanisms contributing to the expansion of an NFκB + cell population on ET are unknown.