Subject(s)
Actins , Breast Neoplasms , Calgranulin A , Calgranulin B , Cell Movement , Epithelial-Mesenchymal Transition , Humans , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/genetics , Female , Actins/metabolism , Calgranulin B/metabolism , Calgranulin B/genetics , Calgranulin A/metabolism , Calgranulin A/genetics , Cell Line, Tumor , Neoplasm Invasiveness , Receptor for Advanced Glycation End Products/metabolism , Receptor for Advanced Glycation End Products/genetics , PolymerizationABSTRACT
Erratum to: Breast Cancer Res Treat (2013),142:297309,DOI 10.1007/s10549-013-2737-1.In the original publication, the images in Fig. 3 were mistakenly selected from other experiments in which similar procedures were performed. The corrected Fig. 3 is given in this erratum.
ABSTRACT
S100A8/A9 proteins are members of EF-hand calcium-binding proteins secreted by neutrophils and activated monocytes. S100A8/A9 has cell growth-promoting activity at low concentrations by binding to the receptor for advanced glycation end products (RAGE). In this study, we report for the first time that S100A8/A9 promoted the invasion of breast cancer cells depending on RAGE. In addition, RAGE binding to S100A8/A9 promoted the phosphorylation of LIN-11, Isl1, and MEC-3 protein domain kinase, as well as cofilin. This phosphorylation is a critical step in cofilin recycling and actin polymerization. Interestingly, RAGE binding to S100A8/A9 enhanced cell mesenchymal properties and induced epithelial-mesenchymal transition. Mechanistically, RAGE binding to S100A8/A9 stabilized Snail through the NF-κB signaling pathway. Based on these observations, RAGE expression in breast cancer cells was associated with lymph node and distant metastases in patients with invasive ductal carcinoma. Moreover, RAGE binding to S100A8/A9 promoted lung metastasis in vivo. In summary, our in vitro and in vivo results indicated that RAGE binding to S100A8/A9 played an important role in breast cancer invasion/metastasis. This study identified both RAGE and S100A8/A9 as potential anti-invasion targets for therapeutic intervention in breast cancer.
Subject(s)
Actins/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Calgranulin A/metabolism , Calgranulin B/metabolism , Epithelial-Mesenchymal Transition , Receptors, Immunologic/metabolism , Actin Depolymerizing Factors/metabolism , Animals , Carcinoma, Ductal, Breast/metabolism , Carcinoma, Ductal, Breast/pathology , Cell Line, Tumor , Cell Movement , Female , Humans , LIM-Homeodomain Proteins/metabolism , Mice , Mice, Inbred NOD , Middle Aged , NF-kappa B/metabolism , Phosphorylation , Polymerization , Receptor for Advanced Glycation End Products , Transcription Factors/metabolism , Xenograft Model Antitumor AssaysABSTRACT
Chemokine (C-C motif) ligand 18 (CCL18), which is derived from tumour-associated macrophages (TAMs), plays a critical role in promoting breast cancer metastasis via its receptor, PYK2 N-terminal domain interacting receptor 1 (Nir1). However, the molecular mechanism by which Nir1 promotes breast cancer metastasis by binding to CCL18 remains elusive. In this study, Nir1 expression was associated with lymph node and distant metastasis in patients with invasive ductal carcinoma. For the first time, we report that Nir1 binding to CCL18 promotes the phosphorylation of Akt, LIN-11, Isl1 and MEC-3 protein domain kinase (LIMK), and cofilin, which is a critical step in cofilin recycling and actin polymerisation. Interestingly, Nir1 binding to CCL18 can enhance cell mesenchymal properties and induce epithelial-mesenchymal transition (EMT). Mechanistically, Nir1 binding to CCL18 stabilises Snail via the Akt/GSK3ß signalling pathway. In support of these observations, Nir1 binding to CCL18 promoted lung metastasis and LY294002 could inhibit it in vivo. In summary, our in vitro and in vivo results indicate that Nir1 binding to CCL18 plays an important role in breast cancer invasion/metastasis. This study identified both Nir1 and CCL18 as potential anti-invasion targets for therapeutic intervention in breast cancer.
