Nodal-signaling-promotes-a-tumorigenic-phenotype-in-human-breast-cancer_2014_Seminars-in-Cancer.pdfVIP

RN i G J a U b c a K N B p c E 1 t c e a R b p g p 2 h 1Seminars in Cancer Biology 29 (2014) 40–50 Contents lists available at ScienceDirect Seminars in Cancer Biology jo ur nal ho me pag e: www.elsev ier .com/ locate /semcancer eview odal signaling promotes a tumorigenic phenotype n human breast cancer ina Kirsammera, Luigi Strizzi a,b, Naira V. Margaryana, Alina Gilgura, Matthew Hyserc, anis Atkinsonc, Dawn A. Kirschmanna, Elisabeth A. Seftora, Mary J.C. Hendrixa,b,? Cancer Biology and Epigenomics Program, Ann and Robert H. Lurie Children’s Hospital of Chicago Research Center, 2430 N Halsted St., Chicago, IL 60614, nited States Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States Presence Saint Francis Hospital, 355 Ridge Ave, Evanston, IL 60202, United States r t i c l e i n f o eywords: odal reast cancer 27 -myc RK a b s t r a c t The Ras-ERK pathway is deregulated in approximately a third of human cancers, particularly those of epithelial origin. In aggressive, triple-negative, basal-like breast cancers, most tumors display increased MEK and ERK phosphorylation and exhibit a gene expression profile characteristic of Kras or EGFR mutant tumors; however, Ras family genetic mutations are uncommon in triple-negative breast cancer and EGFR mutations account for only a subset of these tumors. Therefore, the upstream events that activate MAPK signaling and promote tumor aggression in triple-negative breast cancers remain poorly defined. We have previously shown that a secreted TGF- family signaling ligand, Nodal, is expressed in breast cancer in correlation with disease progression. Here we highlight key findings demonstrating that Nodal is required in aggressive human breast cancer cells to activate ERK signaling and downstream tumorigenic p