Abstract P3-01-21: Functional duality of NUAK2 in breast cancer metastases

Abstract Background: Breast cancer patients with lymph nodes metastasis were proven to have more aggressive biologically phenotypes. This study was aimed to find different biomarker ectopic expression between breast cancer patients' metastatic lymph nodes and primary cancer, and to explore the potential molecular mechanisms. Method: From our previous research, we selected the pairing samples from primary breast cancer with their early stage lymph node metastasis to carry out differential gene expression profiling. Genes with high expression level in sentinel lymph node metastasis were obtained. Then according to the findings of CRISPR/Cas9 screening and the results in relevant literature and online public database, we decided to investigate the role of NUAK2 in our further research. In vitro and in vivo analyses were carried out to determine the potential mechanisms of NUAK2 in lymph node metastases and prognosis. Results NUAK2 belongs to the AMP-activated protein kinase (AMPK) family, with its members controling protein metabolism, polarity, and overall cellular homeostasis actin cytoskeleton organization. The effect of NUAK2 variant expression in breast cancer metastases remains unknown. In this study, it was found that the expression level of NUAK2 was significantly higher in 5 paired metastatic lymph node than that in primary cancer, using Affymetrix GeneChip® Human Transcriptome Array 2.0. From online public database, higher NUAK2 expression level was markedly associated with better metastasis-free survival in breast cancer patients. The effects of NUAK2 on proliferation were investigated by CCK-8 and IncuCyte ZOOM™ assay, respectively. The results demonstrated that knockdown NUAK2 was able to significantly inhibit the proliferation of breast cancer cells. However, for cancer metastases, it was demonstrated that knock-down of NUAK2 significantly accelerated the migration of breast cancer cells, while overexpression of NUAK2 notably inhibited breast cancer cell migration. When promoting proliferation of breast cancer cells, NUAK2 might involve signal pathways of cell cycle. As for the anti-metastasis function, it would regulate cell adhesion, cell motility and microenvironment. Conclusion: Our in vitro study demonstrated that NUAK2 has shown reverse effects of tumor cell proliferation and invasion. The interaction of NUAK2 and cancer cells could be an important role in cell proliferation involved in cell cycle signal pathway, and modulate cell mobility by inducing cell-cell detachment. Its molecular mechanism of dual effect in breast cancer need further investigation. Citation Format: Wang Jia, XUE Jingyan, Hou Jianjing, Xiu Bingqiu, Li Lun, Chi Yayun, Wu Jiong. Functional duality of NUAK2 in breast cancer metastases [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-01-21.