Our previous study demonstrates that HER-2/Neu oncogene inhibits a matrix metalloproteinase inhibitor and tumor metastasis suppressor RECK to promote metastasis. Conversely, the effect of RECK on the oncogenic function of HER-2/Neu is unknown. Ectopic expression of RECK in 293T cells and HER-2/Neu-overexpressing breast cancer cells shows that RECK and HER-2/Neu are co-localized and these two proteins can be co-immunoprecipitated. RECK inhibits HER-2/Neu receptor dimerization and autophosphorylation, which causes reduction of ERK and AKT kinase activity and down-regulation of HER-2/Neu target genes. RECK expression is reduced in 58.8% of breast cancer tissues and is associated with lymph node invasion supporting its anti-metastatic role. Collectively, we provide the first evidence that RECK can negatively regulate oncogenic activity of HER-2/Neu by inhibiting receptor dimerization. Structured summary: HER-2/Neu physically interacts with HER-2/Neu by blue native page (View interaction) HER-2/Neu physically interacts with RECK by coimmunoprecipitation (View interaction) HER-2/Neu and RECK colocalize by fluorescence microscopy (View Interaction 1, 2) HER-2/Neu physically interacts with RECK by anti bait coimmunoprecipitation (View interaction) © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Hong, K. J., Hsu, M. C., Hou, M. F., & Hung, W. C. (2011). The tumor suppressor RECK interferes with HER-2/Neu dimerization and attenuates its oncogenic signaling. FEBS Letters, 585(4), 591–595. https://doi.org/10.1016/j.febslet.2011.01.021