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Park et al. J Cancer Metastasis Treat 2019;5:17 I http://dx.doi.org/10.20517/2394-4722.2018.84 Page 11 of 12

into 2 groups with high and low susceptibility to killing by IL-2 activated lymphocytes. The subset with
[31]
low lysablity expressed ICAM-1 at levels 10 fold lower than those of tumor clones with high lysability .
These results suggest that a constitutively high expression of ICAM-1 on tumors would be the parameter
contributing to the high lysability of these tumor cells by any effector.

This study investigated the role of AF1q-attenuated ICAM-1 in progression and metastasis of breast
cancer. Based on published reports, ICAM-1 strongly stimulates metastasis but also regulates lymphocyte
infiltration via interactions between immune cells and malignant cells. This suggests that ICAM-1 needs an
on-off switch for cancer progression and metastasis. It needs “off” to escape from host immune surveillances
system in the initial phase of cancer, but “on” to invade and grow afterwards. Our results suggest that AF1q
is a switch for ICAM-1 expression. Therefore, AF1q is a promising target for developing treatment for breast
cancer metastasis.

DECLARATIONS
Acknowledgments
We thank Sabine Waigel and current member of the Tse lab for technical assistance.

Authors’ contributions
Conception and design: Park J, Tse W
Collectively performed experiments: Park J, Hwang JY, Thore A, Kim S
Statistical analysis: Park J, Hwang JY
Writing, review, and/or revision of the manuscript: Park J, Hwang JY, Togano T, Hagiwara S, Park JW, Tse W

Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on
reasonable request.

Financial support and sponsorship
The work was supported by the start-up funds from James Graham Brown Cancer Center, University of
Louisville, and an award from the Kentucky Lung Cancer Research Foundation to Tse W. Part of this work
was performed with assistance of the UofL Genomics Facility, which is supported by NIH/NIGMS KY-
INBRE (P20GM103436), the James Graham Brown Foundation, and user fees.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2019.

REFERENCES
1. Tse W, Zhu W, Chen HS, Cohen A. A novel gene, AF1q, fused to MLL in t(1;11) (q21;q23), is specifically expressed in leukemic and
immature hematopoietic cells. Blood 1995;85:650-6.
2. Park J, Schlederer M, Schreiber M, Ice R, Merkel O, et al. AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast