Proteomic analysis reveals that CD147/EMMPRIN confers chemoresistance in cancer stem cell‐like cells

• DOI: 10.1002/pmic.201200511
• Publication Date: 2013-04-02T08:04:57Z
• Authors: Min Jueng Kang; Hwang‐Phill Kim; Kyeong‐seob Lee; Young‐Dong Yoo; Yong‐Tae Kwon; Kristine M. Kim; Tae‐You Kim; Eugene C. Yi
• Keywords: Proteomics; 0301 basic medicine; Antimetabolites, Antineoplastic; Glycogen Synthase Kinase 3 beta; Proteome; Cell Survival; Down-Regulation; Membrane Proteins; 3. Good health; Glycogen Synthase Kinase 3; 03 medical and health sciences; Phenotype; Drug Resistance, Neoplasm; Cell Line, Tumor; Gene Knockdown Techniques; Basigin; Neoplastic Stem Cells; Humans; Fluorouracil; RNA, Small Interfering; Proto-Oncogene Proteins c-akt; Cell Proliferation; Signal Transduction

Cancer stem cells (CSCs) are a subpopulation of tumor that can self-renew, metastasize, and promote cancer recurrence. A comprehensive characterization the CSC proteome has been hampered due to their scarcity rapid differentiation. Here, we present systematic analysis cell-surface using CSC-like cell line derived from MDA-MB453 breast cells, which exhibited CD44(+) /CD24(-) (where CD is cluster differentiation) phenotype chemoresistance. We identified differentially expressed proteins in including upregulated plasma membrane such as CD44, CD133, epidermal growth factor receptor (EGFR), CD147, cadherin 1, integrins, catenin (cadherin-associated protein), beta 1 (CTNNB1), an in-situ biotinylation approach followed by MS analysis. examined role CD147 promotion survival, demonstrated inhibition with monoclonal antibody induced significant growth. siRNA-mediated silencing gene expression restored sensitivity 5-fluorouracil (5-FU), along decreasing thymidylate synthase, p-AKT, β-catenin, while increasing p-glycogen synthase kinase (GSK)3β. Increased seen proteomic analysis, functional consequences overexpression suggest may be one critical involved promoting chemoresistance survival CSCs.