blimp1 activation by ap-1 in human lung cancer cells promotes a migratory phenotype and is inhibited by the lysyl oxidase propeptideblimp1激活ap-1在人类肺癌细胞促进迁移表型,赖氨酰化氧前肽的抑制.pdf

Blimp1 Activation by AP-1 in Human Lung Cancer Cells Promotes a Migratory Phenotype and Is Inhibited by the Lysyl Oxidase Propeptide 1. 1. 2 3 1 Ziyang Yu , Seiichi Sato , Philip C. Trackman , Kathrin H. Kirsch , Gail E. Sonenshein * 1 Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts, United States of America, 2 Division of Oral Biology, Boston University Henry M. Goldman School of Dental Medicine, Boston, Massachusetts, United States of America, 3 Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts, United States of America Abstract B lymphocyte-induced maturation protein 1 (Blimp1) is a master regulator of B cell differentiation, and controls migration of primordial germ cells. Recently we observed aberrant Blimp1 expression in breast cancer cells resulting from an NF-kB RelB to Ras signaling pathway. In order to address the question of whether the unexpected expression of Blimp1 is seen in other epithelial-derived tumors, we selected lung cancers as they are frequently driven by Ras signaling. Blimp1 was detected in all five lung cancer cell lines examined and shown to promote lung cancer cell migration and invasion. Interrogation of microarray datasets demonstrated elevated BLIMP1 RNA expression in lung adenocarcinoma, pancreatic ductal carcinomas, head and neck tumors as well as in glioblastomas. Involvement of Ras and its downstream kinase c-Raf was confirmed using mutant and siRNA strategies. We next addressed the issue of mechanism of Blimp1 activation in lung cancer. Using knockdown and ectopic expression, the role of the Activator Protein (AP)-1 family of transcription factors was demonstrated. Further, chromatin immunoprecipitati