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Author Notes:

Correspondence to: Lukas Kenner, email: lukas.kenner@lbicr.lbg.ac.at William Tse, email: william.tse@louisville.edu

Conception and design: J.Park, C.Ji, L.F.Gibbson, Y.Rojanasakul, S.Remick, A.Ivanov, E.Pugacheva, K.D.Bunting, R.Moriggle, L.Kenner and W.Tse

Collectively performed experiments: J.Park, M.Schreiber, R.Ice, S.Kim, J.Addison, J.Zou, S.T.Bunting, Z.Wang, Z.B.Horvath, G.Huang, O.Merkel and M.Schlederer

Statistical analysis in patient cohort: S.Hofbauer

Writing, review, and/or revision of the manuscript: J.Park, C.Ji, L.F.Gibbson, Y.Rojanasakul, S.Remick, A.Ivanov, E.Pugacheva, K.D.Bunting, R.Moriggl, L.Kenner and W.Tse

We thank Helen Kim for her excellent editorial assistance.

This work is dedicated to Clara Kenner and many other breast cancer patients.

The authors disclose no potential conflict of interest.


Research Funding:

This work was partly supported by the Career Development Award (CDA) from the American Society of Clinical Oncology, the John Hartford Foundation, and the T. Franklin William Scholar Program from the Association of Specialty Professors (WT).

This work was supported by grants from NIH/NCI (R01CA148671 to EP; 5P20RR016440 in part to AI) and the Susan G. Komen Foundation (KG110350 to AI; KG100539 to EP).

RM was supported by SFB-F2807/SFB-F4707, from the Austrain ScienceFund (FWF).

LK was supported by project P26011 from FWF and by Oncotyrol.

Animal Models & Imaging Facility has been supported by the MBRCC and NIH grants P20 RR016440, P30 RR032138/GM103488 and S10RR026378.

Flow Cytometry Facility was supported by MBRCC CoBRE, ARIA S10, Fortess S10 and WV InBRE grant GM103488/RR032138, RR020866, OD016165 and GM103434.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • Cell Biology
  • AF1q
  • TCF7
  • CD44
  • Wnt
  • metastasis

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

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Journal Title:



Volume 6, Number 24


, Pages 20697-20710

Type of Work:

Article | Final Publisher PDF


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 MDAdemonstrate 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.

Copyright information:

© 2015 Park et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/).

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