TY - JOUR AU - Artibani, Mara AU - Masuda, Kenta AU - Hu, Zhiyuan AU - Rauher, Pascal C. AU - Mallett, Garry AU - Wietek, Nina AU - Morotti, Matteo AU - Chong, Kay AU - KaramiNejadRanjbar, Mohammad AU - Zois, Christos E. AU - Dhar, Sunanda AU - El-Sahhar, Salma AU - Campo, Leticia AU - Blagden, Sarah P. AU - Damato, Stephen AU - Pathiraja, Pubudu N. AU - Nicum, Shibani AU - Gleeson, Fergus AU - Laios, Alexandros AU - Alsaadi, Abdulkhaliq AU - Santana Gonzalez, Laura AU - Motohara, Takeshi AU - Albukhari, Ashwag AU - Lu, Zhen AU - Bast, Robert C., Jr. AU - Harris, Adrian L. AU - Ejsing, Christer S. AU - Klemm, Robin W. AU - Yau, Christopher AU - Sauka-Spengler, Tatjana AU - Ahmed, Ahmed Ashour T1 - Adipocyte-like signature in ovarian cancer minimal residual disease identifies metabolic vulnerabilities of tumor-initiating cells PY - 2021/06/08/ AB - Similar to tumor-initiating cells (TICs), minimal residual disease (MRD) is capable of reinitiating tumors and causing recurrence. However, the molecular characteristics of solid tumor MRD cells and drivers of their survival have remained elusive. Here we performed dense multiregion transcriptomics analysis of paired biopsies from 17 ovarian cancer patients before and after chemotherapy. We reveal that while MRD cells share important molecular signatures with TICs, they are also characterized by an adipocyte-like gene expression signature and a portion of them had undergone epithelial-mesenchymal transition (EMT). In a cell culture MRD model, MRD-mimic cells showed the same phenotype and were dependent on fatty acid oxidation (FAO) for survival and resistance to cytotoxic agents. These findings identify EMT and FAO as attractive targets to eradicate MRD in ovarian cancer and make a compelling case for the further testing of FAO inhibitors in treating MRD. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.147929 VL - 6 IS - 11 UR - https://doi.org/10.1172/jci.insight.147929 PB - The American Society for Clinical Investigation ER -