AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis

• DOI: 10.18632/oncotarget.4136
• Publication Date: 2015-09-15T04:50:22Z
• Authors: Jino Park; Michaela Schlederer; Martin Schreiber; Ryan Ice; Olaf Merkel; Martin Bilban; Sebastian Hofbauer; Soojin Kim; Joseph Addison; Jie Zou; Chunyan Ji; Silvia T. Bunting; Zhengqi Wang; Menachem Shoham; Gang Huang; Zsuzsanna Bago-Ho...; Laura F. Gibson; Yon Rojanasakul; Scot Remick; Alexey Ivanov; Elena Pugacheva; Kevin D. Bunting; Richard Moriggl; Lukas Kenner; William Tse
• Keywords: 0301 basic medicine; Molecular Sequence Data; Breast Neoplasms; Cell Growth Processes; Mice, SCID; Transfection; Neoplasm Proteins; 3. Good health; Mice; 03 medical and health sciences; Hyaluronan Receptors; Cell Movement; Mice, Inbred NOD; Cell Line, Tumor; Proto-Oncogene Proteins; T Cell Transcription Factor 1; Animals; Heterografts; Humans; Female; Neoplasm Invasiveness; Amino Acid Sequence; Neoplasm Metastasis

// Jino Park 1 , Michaela Schlederer 2,12 Martin Schreiber 3 Ryan Ice 4,5 Olaf Merkel 6 Bilban 7 Sebastian Hofbauer Soojin Kim Joseph Addison Jie Zou 8 Chunyan Ji Silvia T. Bunting 9 Zhengqi Wang Menachem Shoham 10 Gang Huang 11 Zsuzsanna Bago-Horvath 12 Laura F. Gibson 4 Yon Rojanasakul 4,13 Scot Remick Alexey Ivanov Elena Pugacheva Kevin D. Richard Moriggl 2,14 Lukas Kenner 2,12,15,* and William Tse 1,* James Graham Brown Cancer Center, Division of Blood Bone Marrow Transplantation, Department Medicine, University Louisville School Louisville, KY, USA 2 Ludwig Boltzmann Institute for Research, Vienna, Austria Comprehensive Medical Mary Babb Randolph West Virginia Health Science Morgantown, WV, 5 Biochemistry, National Center Tumor Diseases, German Research Heidelberg, Germany Laboratory Vienna Core Facility Genomics, Facilities, Hematology, Qilu Hospital, Shandong Jinan, Shandong, PR China Aflac Disorders Children’s Healthcare Atlanta Emory Atlanta, GA, Case Western Cleveland, OH, Cincinnati Hospital Cincinnati, Clinical Pathology, 13 Pharmaceutical Science, 14 Animal Breeding Genetics, Veterinary Medicine 15 Unit Pathology Animals (UPLA), * These authors have contributed equally to this work Correspondence to: Kenner, email: Tse, Keywords : AF1q, TCF7, CD44, Wnt, metastasis Received March 02, 2015 Accepted April 21, Published June 07, Abstract AF1q is an MLL fusion partner that was identified from acute myeloid leukemia (AML) patients with t (1; 11) (q21; q23) chromosomal abnormality. The function not yet fully known, however, elevated expression associated poor clinical outcomes in various malignancies. Here, we show specifically binds T-cell-factor-7 (TCF7) the Wnt signaling pathway results transcriptional activation CD44 as well multiple downstream targets TCF7/LEF1. In addition, enhanced promotes breast cancer cell proliferation, migration, mammosphere formation, chemo-resistance. xenograft models, enforced cells also liver lung colonization. a cohort 63 patients, higher percentages AF1q-positive primary sites were significantly poorer overall survival (OS), disease-free (DFS), brain metastasis-free (b-MFS). Using paired primary/metastatic samples same demonstrate become dynamically dominant metastatic compared sites. Our findings indicate hyperactive AF1q/TCF7/CD44 regulatory axis may represent “metastatic founder cells” which invasive properties.