Zurück zur Übersicht
| Oncotarget. 2015 Jun 7. pii: 4136 |
| AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis. |
| Park J1, Schlederer M2, Schreiber M3, Ice R4, Merkel O5, Bilban M6, Hofbauer S7, Kim S8, Addison J9, Zou J10, Ji C11, Bunting ST12, Wang Z13, Shoham M14, Huang G15, Bago-Horvath Z16, Gibson LF17, Rojanasakul Y18, Remick S19, Ivanov A20, Pugacheva E21, Bunting KD22, Moriggl R23, Kenner L24, Tse W25 |
 Author information
|
|
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 of AF1q is not yet fully known, however, elevated AF1q expression is associated with poor clinical outcomes in various malignancies. Here, we show that AF1q specifically binds to T-cell-factor-7 (TCF7) in the Wnt signaling pathway and results in transcriptional activation of CD44 as well as multiple downstream targets of the TCF7/LEF1. In addition, enhanced AF1q expression promotes breast cancer cell proliferation, migration, mammosphere formation, and chemo-resistance. In xenograft models, enforced AF1q expression in breast cancer cells also promotes liver metastasis and lung colonization. In a cohort of 63 breast cancer patients, higher percentages of AF1q-positive cancer cells in primary sites were associated with significantly poorer overall survival (OS), disease-free survival (DFS), and brain metastasis-free survival (b-MFS). Using paired primary/metastatic samples from the same patients, we demonstrate that AF1q-positive breast cancer cells become dynamically dominant in the metastatic sites compared to the primary sites. Our findings indicate that breast cancer cells with a hyperactive AF1q/TCF7/CD44 regulatory axis in the primary sites may represent "metastatic founder cells" which have invasive properties. |
|
KEYWORDS: AF1q, CD44, TCF7, Wnt, metastasis |
|
Publikations ID: 26079538 Quelle: öffnen |
Author information
Schnellinfo
-- Cancer Care
-- Kliniken und Partner
-- CCC Cancer School
-- Young CCC
-- CCC Tumorboards
-- CCC Forschungscluster
-- CCC Units
-- CCC Platforms
-- SOPs / Leitlinien
-- Kontakt
Featured
