Joseph W Franses, Julia Philipp, Pavlos Missios, Irun Bhan, Ann Liu, Chittampalli Yashaswini, Eric Tai, Huili Zhu, Matteo Ligorio, Benjamin Nicholson, Elizabeth M Tassoni, Niyati Desai, Anupriya S Kulkarni, Annamaria Szabolcs, Theodore S Hong, Andrew S Liss, Carlos Fernandez-Del Castillo, David P Ryan, Shyamala Maheswaran, Daniel A Haber, George Q Daley, David T Ting
Pancreatic ductal adenocarcinoma (PDAC) lethality is due to metastatic dissemination. Characterization of rare, heterogeneous circulating tumor cells (CTCs) can provide insight into metastasis and guide development of novel therapies. Using the CTC-iChip to purify CTCs from PDAC patients for RNA-seq characterization, we identify three major correlated gene sets, with stemness genes LIN28B/KLF4, WNT5A, and LGALS3 enriched in each correlated gene set; only LIN28B CTC expression was prognostic. CRISPR knockout of LIN28B-an oncofetal RNA-binding protein exerting diverse effects via negative regulation of let-7 miRNAs and other RNA targets-in cell and animal models confers a less aggressive/metastatic phenotype...
July 3, 2020: Nature Communications