title: NHERF1 Enhances Cisplatin Sensitivity in Human Cervical Cancer Cells.
abstract: Cervical cancer is one of the most common female malignancies, and cisplatin-based chemotherapy is routinely utilized in locally advanced cervical cancer patients. However, resistance has been the major limitation. In this study, we found that Na⁺/H⁺ Exchanger Regulatory Factor 1 (NHERF1) was downregulated in cisplatin-resistant cells. Analysis based on a cervical cancer dataset from The Cancer Genome Atlas (TCGA) showed association of NHERF1 expression with disease-free survival of patients received cisplatin treatment. NHERF1 overexpression inhibited proliferation and enhanced apoptosis in cisplatin-resistant HeLa cells, whereas NHERF1 knockdown had inverse effects. While parental HeLa cells were more resistant to cisplatin after NHERF1 knockdown, NHERF1 overexpression in CaSki cells promoted cisplatin sensitivity. Overexpression and knockdown studies also showed that NHERF1 significantly inhibited AKT and extracellular signal-regulated kinase (ERK) signaling pathways in cisplatin-resistant cells. Taken together, our results provide the first evidence that NHERF1 can sensitize cisplatin-refractory cervical cancer cells. This study may help to increase understanding of the molecular mechanisms underlying cisplatin resistance in tumors.
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China. taotaotxwd@ccmu.edu.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Tao
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China. xmyang126@126.com.|Beijing International Cooperation Base for Science and Technology on China-UK Cancer Research, Beijing 100069, China. xmyang126@126.com.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China. qqin777@163.com.|Beijing International Cooperation Base for Science and Technology on China-UK Cancer Research, Beijing 100069, China. qqin777@163.com.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Qin
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China. shiwen137523@163.com.|Experiment Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China. shiwen137523@163.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China. wangqiqi3127@126.com.
authors.forename: Qiqi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Core Facilities Center, Capital Medical University, Beijing 100069, China. yy2012@ccmu.edu.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China. jq_he@ccmu.edu.cn.|Beijing International Cooperation Base for Science and Technology on China-UK Cancer Research, Beijing 100069, China. jq_he@ccmu.edu.cn.
authors.forename: Junqi
authors.initials: J
authors.lastname: He
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; C093376:sodium-hydrogen exchanger regulatory factor; D002945:Cisplatin
keywords: NHERF1; cervical cancer; cisplatin resistance