Mechanisms regulating stem cell properties and immune interplay of tumor-initiating cells
Speaker: Toni Celià-Terrassa, PhD. Department of Molecular Biology, Princenton University, NJ (USA)
Organizer: IRB Barcelona
Date: Thursday, February 23, 12.00h
Place: Aula Fèlix Serratosa, Parc Científic de Barcelona, Spain
Host: Dr. Eduard Batlle, IRB Barcelona
Tumor-initiating cells (TICs), or cancer stem cells (CSC), possess stem cell-like properties observed in normal adult tissue stem cells. Epithelial mesenchymal transition (EMT) has long been considered as the main transformation promoting stem cell properties in cancer cells, however we observed that the reverse transition can also engage such properties during metastatic colonization. Additionally, we show how the spatiotemporal dynamics of EMT can generate distinct EMT gene programs with different metastatic capability. Besides EMT, we are also seeking for other regulatory mechanisms of cell plasticity, maintaining self-renewing capacity and resisting differentiation elicited by cell-intrinsic or microenvironmental cues. We have found that miR-199a promotes stem cell properties in mammary stem cells (MaSCs) and breast CSCs by directly repressing nuclear receptor corepressor LCOR, which primes interferon (IFN) sensitivity. Elevated miR-199a expression in stem cell-enriched populations protects normal and malignant stem-like cells from differentiation and senescence induced by IFNs that are produced by immune cells in the mammary gland. Importantly, the miR-199a-LCOR-IFN axis is activated in poorly differentiated ER- breast tumors, functionally promotes tumor initiation and metastasis, and is associated with poor clinical outcome. This study reveals a common mechanism shared by normal and malignant stem cells to protect them from suppressive immune cytokine signaling and facilitate TIC abilities.
Oncology Programme Seminar