Drugs, Bugs, and Cancer: Fusobacterium nucleatum Promotes Chemoresistance in Colorectal Cancer  Azucena Ramos, Michael T. Hemann  Cell  Volume 170, Issue 3, Pages 411-413 (July 2017) DOI: 10.1016/j.cell.2017.07.018 Copyright © 2017 Terms and Conditions

Figure 1 Mechanisms by which Cancer Cells Co-Opt Inherent or Drug-Induced Features of the TME to Survive Therapy (A) Upon DNA damage induced by doxorubicin, endothelial cells in the thymus release cytokines that generate a chemo-protective niche, allowing lymphoma cells resident in this organ to survive therapy. (B) Therapy-induced tissue damage can induce the recruitment of both tissue-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) that promote tumor cell survival by the secretion of soluble factors and by dampening anti-tumor immune responses. (C) In the bone marrow, leukemic cells can interact with intrinsic features of the TME, such as the extracellular matrix (ECM), via integrin receptors. This interaction has been shown to induce a cell-adhesion-mediated drug resistance (CAM-DR) phenotype, including the upregulation of multiple drug resistance (MDR) pumps and increased signaling through pro-survival pathways. OB, osteoblast; OC, osteoclast. (D) Yu et al. present a novel mechanism by which the TME promotes chemoresistance in this issue of Cell. The TLR4 and MYD88 signaling pathway is essential for Fusobacterium nucleatum (Fn) infection. CRC cells resident in the gut can co-opt this colonization property by interacting with Fn. TLR4/MYD88 activation by this microbe downregulates miRNA-18a∗ and miRNA-4082, inducing a switch from apoptosis to autophagy in CRC cells and allowing them to survive therapy. Cell 2017 170, 411-413DOI: (10.1016/j.cell.2017.07.018) Copyright © 2017 Terms and Conditions