title: Proteomic analysis reveals that CD147/EMMPRIN confers chemoresistance in cancer stem cell-like cells.
abstract: Cancer stem cells (CSCs) are a subpopulation of tumor cells that can self-renew, metastasize, and promote cancer recurrence. A comprehensive characterization of the CSC proteome has been hampered due to their scarcity and rapid differentiation. Here, we present a systematic analysis of the cell-surface proteome using a CSC-like cell line derived from MDA-MB453 breast cancer cells, which exhibited a CD44(+) /CD24(-) (where CD is cluster of differentiation) phenotype and chemoresistance. We identified differentially expressed proteins in CSC-like cells, including upregulated plasma membrane proteins such as CD44, CD133, epidermal growth factor receptor (EGFR), CD147, cadherin 1, integrins, and catenin (cadherin-associated protein), beta 1 (CTNNB1), using an in-situ biotinylation approach followed by MS analysis. We examined the role of CD147 in the promotion of CSC growth and survival, and demonstrated that inhibition of CD147 with a monoclonal antibody induced significant inhibition of cell growth. siRNA-mediated silencing of CD147 gene expression restored the sensitivity of CSC-like cells to 5-fluorouracil (5-FU), along with decreasing the expression of thymidylate synthase, p-AKT, and β-catenin, while increasing the expression of p-glycogen synthase kinase (GSK)3β. Increased CD147 expression in the CSC-like cells, as seen by proteomic analysis, and the functional consequences of CD147 overexpression in CSC-like cells suggest that CD147 may be one of the critical cell-surface proteins involved in promoting chemoresistance and survival in CSCs.
authors.affiliation: WCU Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine or College of Pharmacy, Seoul National University, Seoul, South Korea.
authors.forename: Min Jueng
authors.initials: MJ
authors.lastname: Kang
authors.forename: Hwang-Phill
authors.initials: HP
authors.lastname: Kim
authors.forename: Kyeong-seob
authors.initials: KS
authors.lastname: Lee
authors.forename: Young-Dong
authors.initials: YD
authors.lastname: Yoo
authors.forename: Yong-Tae
authors.initials: YT
authors.lastname: Kwon
authors.forename: Kristine M
authors.initials: KM
authors.lastname: Kim
authors.forename: Tae-You
authors.initials: TY
authors.lastname: Kim
authors.forename: Eugene C
authors.initials: EC
authors.lastname: Yi
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D051926:Basigin / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D020543:Proteome / Q000378:metabolism; D040901:Proteomics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D000964:Antimetabolites, Antineoplastic; C497886:BSG protein, human; D008565:Membrane Proteins; D020543:Proteome; D034741:RNA, Small Interfering; D051926:Basigin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D005472:Fluorouracil