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Triple-negative breast cancers (TNBCs) are characterized by low overall survival and poor response to therapy because of their aggressiveness and limited available treatments. We found a subset of TNBC expressing the master regulator estrogen receptor beta (ERβ1) and characterized the effect of this nuclear receptor in human TNBC cells by a multiomics approach. Results highlight transcriptome deregulation by ERβ involving association with chromatin remodeling complexes, including PRC1/2, and provide an explanation for its oncosuppressive effects on TNBC cells.

Interleukin‐8 (IL‐8/CXCL8) mediates its biological effects through two receptors, CXCR1 and CXCR2. While CXCR1 recognizes IL‐8 and granulocyte chemotactic protein‐2, CXCR2 binds to multiple chemokines including IL‐8, CXCL1, 2 and 3. Both IL‐8 and CXCL1 have been implicated in the neoplastic features of thyroid cancer (TC). Here, we assessed the role of the autocrine circuits sustained by IL‐8 and CXCL1 in determining TC stem cell (TC SC) features. Using immunohistochemistry, we found that thyroid epithelial cancerous, but not normal, cells stained positive for IL‐8, whose levels correlated with lymph‐nodal metastases. We assessed the expression of endogenous IL‐8 and CXCL1, by ELISA assays, and of their receptors CXCR1 and CXCR2, by flow cytometry, in a panel of TC cell lines. These molecules were expressed in TC cell lines grown in adherence, and at higher levels also in thyrospheres enriched in stem‐like cells. RNA interference demonstrated that IL‐8/CXCR1, but not CXCL1/CXCR2, is crucial for the sphere‐forming, self‐renewal and tumor‐initiating ability of TC cells. Accordingly, treatment of TC cells with IL‐8, but not with CXCL1, potentiated cell stemness. We identified CD34 as an IL‐8‐induced gene and as a TC SC marker, since it was overexpressed in thyrospheres compared to adherent cells. Moreover, CD34 is required for the efficient sphere‐forming ability and tumorigenicity of TC cells. Our data indicate that IL‐8, but not the CXCL1 circuit, is critical for the regulation of TC SCs, and unveils novel potential targets for the therapy of as yet untreatable forms of TC. StemCells2017;35:135–146 IL‐8 is critical for the sphere formation, self‐renewal and tumor‐initiating ability of thyroid cancer stem cells. Targeting the IL‐8/CXCR1 circuit could be exploited as a novel therapeutic strategy for patients with untreatable thyroid carcinoma.

Aim and background It has been recently demonstrated that the detection of stem cell niches in triple-negative (TN) breast cancer may provide good prognostic clues for this tumor.Methods and study design We investigated the subcellular expression and localization of the cancer stem cell marker CD133 in a TN breast cancer biopsy from a 42-year-old Caucasian woman with a histological diagnosis of high-grade invasive ductal breast carcinoma by immunohistochemistry, flow cytometry and quantitative real-time PCR (qRT-PCR).Results We describe for the first time in a TN breast cancer the nuclear mislocalization of CD133, which normally shows membrane localization and more sporadically cytoplasmic localization. We also found this aberrant expression with qRT-PCR analysis but not flow cytometry.Conclusions Nuclear localization of CD133 may be an indicator of poor prognosis in TN breast cancer, as it is known that surface molecules, when moving into the nucleus, can act as transcriptional regulators by interfering with molecular pathways directly connected to the proliferation and differentiation of tumor cells.