CIAPIN1 targets Na⁺/H⁺ exchanger 1 to mediate MDA-MB-231 cells' metastasis through regulation of MMPs via ERK1/2 signaling pathway.
Cytokine-induced antiapoptotic inhibitor 1 (CIAPIN1) was recently identified as an essential downstream effector of the Ras signaling pathway and has been confirmed to be closely associated with various malignant tumors. However, its potential role in regulating breast cancer metastasis remains unclear. Matrix metalloproteinases (MMPs) are a broad family of zinc-biding endopeptidases that participate in the extracellular matrix (ECM) degradation that accompanies cancer cell invasion, metastasis and angiogenesis. In this study, we found up-regulation of CIAPIN1 by lentiviral expression vector inhibited the migration, invasion and MMPs expression of MDA-MB-231 cells. Further, CIAPIN1 over-expression decreased NHE1 (Na(+)/H(+) exchanger 1) expression and ERK1/2 phosphorylation. Importantly, treating CIAPIN1 over-expressed MDA-MB-231 cells with the NHE1 specific inhibitor, Cariporide, further inhibited the metastatic capacity, MMPs expression and phosphorylated ERK1/2. Treatment with the MEK1 specific inhibitor, PD98059, induced nearly the same suppression of CIAPIN1 over-expression-dependent migration, invasion and MMPs expression as was observed with Cariporide. Further, Cariporide and PD98059 synergistically suppressed migration, invasion and MMPs expression of CIAPIN1 over-expressed MDA-MB-231 cells. Thus, our results revealed the mechanism by which CIAPIN1 targeted NHE1 to mediate migration and invasion of MDA-MB-231 cells through regulation of MMPs via ERK1/2 signaling pathway.
State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing Road 288, Tianjin 300020, China; Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin 300060, China.
Jian
J
Wang
State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing Road 288, Tianjin 300020, China.
Hua
H
Xu
State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing Road 288, Tianjin 300020, China.
Qi
Q
Wang
State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing Road 288, Tianjin 300020, China.
Hairui
H
Zhang
State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing Road 288, Tianjin 300020, China.
Yani
Y
Lin
State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing Road 288, Tianjin 300020, China.
Hongju
H
Zhang
State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing Road 288, Tianjin 300020, China.
Qinghua
Q
Li
State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing Road 288, Tianjin 300020, China. Electronic address: pang@ihcams.ac.cn.
Tianxiang
T
Pang
D027682:Cation Transport Proteins / Q000378:metabolism*; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D061986:MCF-7 Cells; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*
C489114:CIAPIN1 protein, human; D027682:Cation Transport Proteins; D047908:Intracellular Signaling Peptides and Proteins; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D020782:Matrix Metalloproteinases
CIAPIN1; ERK1/2; Invasion; MMPs; Migration; NHE1