title: SKA1 regulates the metastasis and cisplatin resistance of non-small cell lung cancer.
abstract: Currently, chemotherapy with platinum-based drugs including cisplatin is the most effective therapy for the treatment of non-small cell lung carcinoma (NSCLC). However, the efficacy of chemotherapy is limited due to commonly developed drug resistance. Spindle and kinetochore-associated complex subunit 1 (SKA1) is part of a complex essential for stabilizing the attachment of spindle microtubules to kinetochores and for maintaining the metaphase plate during mitosis. In the present study, we aimed to investigate the role of SKA1 in the process of metastasis and drug resistance of NSCLC. We completed a series of experiments to investigate the function of SKA1 in NSCLC metastasis and drug resistance including qRT-PCR, immunohistochemistry and western blotting, as well as MTT, BrdU, wounded healing, Transwell and gelatin zymography assays. We demonstrated that the expression levels of SKA1 were elevated in NSCLC and were correlated with cancer progression and malignancy. We also reported that SKA1 positively regulated the proliferation and metastatic ability of NSCLC cells. In addition, we determined that SKA1 contributed to cisplatin resistance in NSCLC cells by protecting these cells from cisplatin-induced cell apoptosis. SKA1 also appeared to regulate the ERK1/2 and the Akt-mediated signaling pathways in NSCLC cells. SKA1 is required for metastasis and cisplatin resistance of non-small cell lung cancer.
authors.affiliation: Department of Anaesthesia, Critical Care and Pain Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Respiratory Diseases, Tianjin First Center Hospital, Tianjin 300192, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Anaesthesia, Critical Care and Pain Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
authors.forename: Qionghua
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Department of Anaesthesia, Critical Care and Pain Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Anaesthesia, Critical Care and Pain Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
authors.forename: Changhong
authors.initials: C
authors.lastname: Miao
authors.affiliation: Department of Anaesthesia, Critical Care and Pain Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
authors.forename: Biao
authors.initials: B
authors.lastname: Zhu
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D016022:Case-Control Studies; D002465:Cell Movement; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology*; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D002868:Chromosomal Proteins, Non-Histone; C516427:SKA1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin