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Page 2 of 12 Park et al. J Cancer Metastasis Treat 2019;5:17 I http://dx.doi.org/10.20517/2394-4722.2018.84

affected the attachment of T cells to a breast cancer cell monolayer. We confirmed the finding by performing the
analysis on Burkitt’s lymphoma.

Conclusion: Attenuation of ICAM-1 by AF1q on tumor cells disadvantages host anti-tumor defenses through the
trafficking of lymphocytes, which affects tumor progression and metastasis.

Keywords: MLLT11, AF1q, intercellular adhesion molecule-1, breast cancer, metastasis, RNA-sequencing

INTRODUCTION
While primary lesion breast tumors are not fatal to the patient, the metastatic breast tumors are. For this
reason, breast patients are often given other treatments after surgery to try to eliminate metastatic tumor
cells that might have spread to other organs. Although the prognosis for breast cancer has improved during
the last decade, we still lack specific treatments that target metastases. The discovery of such treatment will
be of great benefit to patients.

The AF1q gene, located in chromosome 1, band 21, is an MLL fusion partner that was identified in acute
[1]
myeloid leukemia 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. We have demonstrated that the enhanced AF1q expression promotes cell proliferation,
[2]
migration, sphere formation, and chemo-resistance in vitro and in vivo breast cancer models . During the
course of our study, we made an exciting discovery that AF1q physically interacts with TCF7, a key factor in
[2]
the Wnt signaling pathway that enhances its activation . The Wnt signaling pathway plays a leading role in
various processes that are important for cancer progression, including cancer initiation, growth, cell death,
[3]
differentiation, and metastasis . Strikingly, we observed that AF1q-positive cancer cells are significantly
more prevalent at metastatic sites than in primary breast tumors, when comparing paired samples from
[2]
breast cancer patients . Moreover, the Wnt signaling pathway was activated by AF1q crosstalk to the STAT3
[4]
pathway via the PDGF/PDGFR cascade . The PDGF-B/PDGFR signaling cascade was activated upon
enforced AF1q expression and this caused an increase in STAT3 DNA binding activity through Src kinase
[4]
action in cancer cells . Moreover, AF1q is one of the genes that are differentially expressed between highly
[2]
metastatic breast cancer cells and their parent cells . Importantly, when breast tumor cells were treated
with doxorubicin or etoposide, endogenous AF1q expression was further activated, implying that current
chemotherapeutics may increase the risk of metastasis of breast cancer. Taken together, characterization
of AF1q-induced breast cancer and new treatment strategies for hyperactive AF1q expression patients are
urgently needed.

Intercellular adhesion molecule-1 (ICAM-1) plays a key role in inflammatory conditions, nervous system
[5,6]
development, and immune response through antigen recognition and lymphocyte surveillances . There
is still controversy regarding the contribution of ICAM-1 expression to tumor progression. Expression of
ICAM-1 on tumor cells negatively correlates with tumor progression and development, including tumor
[7]
size and lymph node metastasis . A better prognosis was also reported for patients with ICAM-1 positive
[8,9]
tumors compared with ICAM-1 negative tumors . However, in vitro studies demonstrated that ICAM-1
[10]
overexpression can positively affect tumorigenicity . Despite the controversy, it is clear that ICAM-1 plays
a pivotal role in immune response. ICAM-1 levels on tumor cells stimulate T-cell receptor-mediated cellular
[11]
immune response . Recent studies revealed that ICAM-1 expression plays an important role in interactions
between lymphokine-activated killer cells and cancer cells [12,13] . These results suggest that a decrease of
ICAM-1 may be one of the mechanisms by which tumor cells escape cell-mediated cytotoxicity and lysis by
the host cellular immune system.