Abstract 3969: AF1q/Mllt11 regulates the expression of intercellular adhesion molecule-1 in breast cancer

Intercellular adhesion molecule-1 (ICAM-1) is a cell surface glycoprotein in the immunoglobulin superfamily. ICAM-1 expression is frequently observed on many cell types including endothelial cells and different cancer cell entities. Experimental data strongly indicate that ICAM-1 can activate intracellular signaling pathways in cancer cells leading to enhanced cell motility, invasion and metastasis. In clinical investigation, however, ICAM-1 expression was negatively correlated to tumor size, lymph node metastasis, and tumor infiltration. Also, there was improved relapse-free and overall survival in patients with ICAM-1 positive tumors. Yet, the function of ICAM-1 expression during malignant progression in breast cancer patients is not understood clearly. However, ICAM-1 is still considered as a breast cancer target and biomarker may lead to the development of a new strategy and platform for breast cancer patients. We observed AF1q, a metastasis enhancer, is only expressed in metastatic cells, MDA-MB-231LN (invasive sub line from MDA-MB-231), not in the primary tumor cells. To investigate whether AF1q has a responsibility in acquisition of metastatic phenotype, we performed RNA-Seq and applied the Metacore network building algorithm. Intriguingly, most genes were directly linked with Intercellular Adhesion Molecule-1 (ICAM-1). Likewise, we identified that ICAM-1 expression is attenuated in MDA-MB-231LN compared to MDA-MB-231. Moreover, the expression of ICAM-1 was negatively regulated, when AF1q was overexpressed in MDA-MD-231LN. Suppressed endogenous AF1q by shRNA could effectively increase the ICAM-1 expression. Attenuation of ICAM-1 by AF1q on tumor cells would disadvantage host anti-tumor defenses by trafficking of lymphocytes, which affect tumor progression and metastasis. We observed that NF-κB activity which regulates ICAM-1 expression is attenuated in response to AF1q expression in breast cancer cells. Published reports shown that Wnt/β-catenin negatively regulates NF-κB activity through protein-protein interaction in colon and breast cancer cells. Previously, we reported that AF1q enhance the TCF7/LEF/β-catenin complex binding affinity as a cofactor. Structurally, AF1q has highly acidic peptide regions highly conserved between species that fulfill the criteria for an acidic blob, a typical feature for cofactors. When we performed immunoprecipitation with NF-κB antibody in MDA-MB-231LN overexpressed AF1q, we observed that β-catenin and AF1q were pulled down together. However, it is not clear yet whether AF1q promote protein interaction between β-catenin and NF-κB. These results suggest that activated β-catenin by AF1q would archive higher affinity to bind with NF-κB and thereby attenuate ICAM-1 expression. Citation Format: Jino Park, Soojin Kim, William Tse. AF1q/Mllt11 regulates the expression of intercellular adhesion molecule-1 in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3969. doi:10.1158/1538-7445.AM2017-3969