SMAD4 represses FOSL1 expression and pancreatic cancer metastatic colonization

• DOI: 10.1016/j.celrep.2021.109443
• Publication Date: 2021-07-27T15:12:25Z
• Authors: Chao Dai; Jonathan P. Rennhack; Taylor E. Arnoff; Maneesha Thaker; Scott T. Younger; John G. Doench; August Yue Huang; Annan Yang; Andrew J. Aguirre; Belinda Wang; Evan Mun; Joyce T. O’Connell; Ying Huang; Katherine Labella; Jessica A. Talamas; Ji Li; Nina Ilic; Justin Hwang; Andrew L. Hong; Andrew O. Giacomelli; Ole Gjoerup; David E. Root; William C. Hahn
• Keywords: 0301 basic medicine; QH301-705.5; PDAC; FOSL1; Adenocarcinoma; colonization; SMAD4; Article; 3. Good health; Gene Expression Regulation, Neoplastic; Pancreatic Neoplasms; Mice; 03 medical and health sciences; Enhancer Elements, Genetic; Cell Line, Tumor; metastasis; Animals; Humans; Biology (General); Neoplasm Metastasis; Proto-Oncogene Proteins c-fos; Carcinoma, Pancreatic Ductal; Cell Proliferation; Smad4 Protein

Metastasis is a complex and poorly understood process. In pancreatic cancer, loss of the transforming growth factor (TGF)-β/BMP effector SMAD4 is correlated with changes in altered histopathological transitions, metastatic disease, and poor prognosis. In this study, we use isogenic cancer cell lines to identify SMAD4 regulated genes that contribute to the development of metastatic colonization. We perform an in vivo screen identifying FOSL1 as both a SMAD4 target and sufficient to drive colonization to the lung. The targeting of these genes early in treatment may provide a therapeutic benefit.