title: Trail resistance induces epithelial-mesenchymal transition and enhances invasiveness by suppressing PTEN via miR-221 in breast cancer.
abstract: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis of cancer cells and is verified effective to various cancers. However, a variety of breast cancer cell lines are resistant to TRAIL and the mechanisms of resistance are largely unknown. In our present experiment, we successfully utilized breast cancer cell line MDA-MB-231 to establish TRAIL-resistant cell line. We found resistance to TRAIL could induce epithelial-mesenchymal transition (EMT) and enhance invasiveness. We further demonstrated PTEN was down-regulated in TRAIL-resistant cells. Silencing miR-221, PTEN expression was up-regulated, the process of EMT could be reversed, and the ability of migration and invasion were correspondingly weakened. We also demonstrated knockdown of miR-221 could reverse resistance to TRAIL partially by targeting PTEN. Our findings suggest that resistance to TRAIL could induce EMT and enhance invasiveness by suppressing PTEN via miR-221. Re-expression of miR-221 or targeting PTEN might serve as potential therapeutic approaches for the treatment of Trail-resistant breast cancer.
authors.affiliation: Department of Oncology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China; Department of Oncology, Affiliated Hospital of Qingdao University Medical College, Qingdao, Shandong Province, China; Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Haiji
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Oncology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China; Department of Oncology, Qingdao Municipal Hospital, Qingdao, Shandong Province, China.
authors.forename: Chunyuan
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Xiangnan
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Oncology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
mesh_terms: D017209:Apoptosis; D001940:Breast / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*
chemical_list: C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D053221:TNF-Related Apoptosis-Inducing Ligand; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human