title: Acquisition of epithelial-mesenchymal transition phenotype and cancer stem cell-like properties in cisplatin-resistant lung cancer cells through AKT/β-catenin/Snail signaling pathway.
abstract: Cisplatin is a first-line chemotherapeutic agent in the treatment of non-small cell lung cancer (NSCLC), but the therapeutic effect is disappointing, partly due to drug resistance. Emerging evidence showed that chemoresistance associates with acquisition of epithelial-mesenchymal transition (EMT) phenotype and cancer stem cell-like properties. However, the underlying mechanism is not entirely clear. In this study, we showed that cisplatin-resistant A549 cells (A549/CDDP) acquire EMT phenotype associated with migratory and invasive capability. A549/CDDP cells also displayed enhanced cancer stem cell-like properties. Increased expression of transcription factor Snail, but not ZEB1, Slug and Twist, was observed in A549/CDDP cells. Knockdown of Snail reversed EMT and significantly attenuated migration, invasion and cancer stem cell-like properties of A549/CDDP cells. Conversely, overexpressed Snail in A549 cells induced EMT and cancer stem cell-like properties. Finally, we demonstrated that activated AKT signal leads to increased β-catenin expression and subsequently up-regulates Snail in A549/CDDP cells. Taken together, these results revealed that AKT/β-catenin/Snail signaling pathway is mechanistically associated with cancer stem cell-like properties and EMT features of A549/CDDP cells, and thus, this pathway could be a novel target for the treatment of NSCLC.
authors: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China. Electronic address: wanghao986118@163.com.
authors: Hao
authors: H
authors: Wang
authors: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors: Ge
authors: G
authors: Zhang
authors: Department of Pharmacology, College of Pharmacy, Jinan University, Guangzhou, China.
authors: Huan
authors: H
authors: Zhang
authors: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors: Fan
authors: F
authors: Zhang
authors: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors: Binhua
authors: B
authors: Zhou
authors: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors: Fen
authors: F
authors: Ning
authors: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors: Hong-Sheng
authors: HS
authors: Wang
authors: Department of Pharmacology, College of Pharmacy, Jinan University, Guangzhou, China. Electronic address: csh5689@sina.com.
authors: Shao-Hui
authors: SH
authors: Cai
authors: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China. Electronic address: dujun@mail.sysu.edu.cn.
authors: Jun
authors: J
authors: Du
mesh_terms: D000970:Antineoplastic Agents; D045744:Cell Line, Tumor; D002945:Cisplatin; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D014411:Neoplastic Stem Cells; D010641:Phenotype; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051176:beta Catenin; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin
keywords: AKT; Cancer stem cell; Cisplatin; EMT; Snail; β-catenin