Nir1 promotes invasion of breast cancer cells by binding to chemokine (C-C motif) ligand 18 through the PI3K/Akt/GSK3β/Snail signalling pathway.

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/GSK3β 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.

Zhang B ，Yin C ，Li H ，Shi L ，Liu N ，Sun Y ，Lu S ，Liu Y ，Sun L ，Li X ，Chen W ，Qi Y ... -  《-》

CCL18 promotes the invasion and metastasis of breast cancer through Annexin A2.

Zhao C ，Zheng S ，Yan Z ，Deng Z ，Wang R ，Zhang B ... -  《-》

CCL18-NIR1 promotes oral cancer cell growth and metastasis by activating the JAK2/STAT3 signaling pathway.

Jiang X ，Huang Z ，Sun X ，Zheng X ，Liu J ，Shen J ，Jia B ，Luo H ，Mai Z ，Chen G ，Zhao J ... -  《BMC CANCER》

CC chemokine ligand 18(CCL18) promotes migration and invasion of lung cancer cells by binding to Nir1 through Nir1-ELMO1/DOC180 signaling pathway.

Non-small cell lung cancer (NSCLC) comprises nearly 80% of lung cancers and the poor prognosis is due to its high invasiveness and metastasis. CC chemokine ligand 18 (CCL18) is predominantly secreted by M2-tumor associated macrophages (TAMs) and promotes malignant behaviors of various human cancer types. In this study, we report that the high expression of CCL18 in TAMs of NSCLC tissues and increased expression of CCL18 in TAMs is correlated with the lymph node metastasis, distant metastasis, and poor prognosis NSCLC patients. CCL18 can increase the invasive ability of NSCLC cells by binding to its receptor Nir1. In addition, CCL18 is capable of modulating cell migration and invasion by regulating the activation of RAC1 which resulted in cytoskeleton reorganization in an ELMO1 dependent manner. Furthermore, we found that CCL18 could enhance adhesion of NSCLC cells via activating ELMO1-integrin β1 signaling. Thus, CCL18 and its downstream molecules may be used as targets to develop novel NSCLC therapy. © 2016 Wiley Periodicals, Inc.

Shi L ，Zhang B ，Sun X ，Zhang X ，Lv S ，Li H ，Wang X ，Zhao C ，Zhang H ，Xie X ，Wang Y ，Zhang P ... -  《-》

Leptin promotes epithelial-mesenchymal transition of breast cancer via the upregulation of pyruvate kinase M2.

Wei L ，Li K ，Pang X ，Guo B ，Su M ，Huang Y ，Wang N ，Ji F ，Zhong C ，Yang J ，Zhang Z ，Jiang Y ，Liu Y ，Chen T ... -  《-》