title: NHE1 mediates migration and invasion of HeLa cells via regulating the expression and localization of MT1-MMP.
abstract: Na(+)/H(+) exchanger 1 (NHE1), acting as an important regulator of intracellular pH (pH(i)) and extracellular pH (pH(e)), has been known to play a key role in the metastasis of many solid tumours. However, the exact mechanism underlying these processes, especially in cervical cancer, is still poorly understood. In the current study, we first showed that the inhibition of NHE1 activity by the specific inhibitor cariporide could suppress migration and invasion of HeLa cells in vitro. Moreover, cariporide also reversed the enhanced migration and invasion in HeLa cells by overexpressed membrane-type 1 matrix metalloproteinase (MT1-MMP). Subsequently, our results showed that NHE1 regulated the expression of MT1-MMP at both messenger RNA and protein levels as well as its localization. Meanwhile, we observed slight modification in the morphology of HeLa cell after treating with cariporide. The present work indicates that NHE1 mediates HeLa cell metastasis via regulating the expression and localization of MT1-MMP and provides a theoretical basis for the development of novel therapeutic strategies targeting cervical cancer.
authors: State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors: Yani
authors: Y
authors: Lin
authors: Jian
authors: J
authors: Wang
authors: Weina
authors: W
authors: Jin
authors: Lihong
authors: L
authors: Wang
authors: Huawen
authors: H
authors: Li
authors: Li
authors: L
authors: Ma
authors: Qinghua
authors: Q
authors: Li
authors: Tianxiang
authors: T
authors: Pang
mesh_terms: D027682:Cation Transport Proteins / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
chemical_list: D027682:Cation Transport Proteins; D006146:Guanidines; D061965:Matrix Metalloproteinase Inhibitors; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14