title: ICAM1 Is a Potential Cancer Stem Cell Marker of Esophageal Squamous Cell Carcinoma.
abstract: Esophageal squamous cell carcinoma (ESCC) accounts for about 90% of esophageal cancer diagnosed in Asian countries, with its incidence on the rise. Cancer stem cell (CSC; also known as tumor-initiating cells, TIC) is inherently resistant to cytotoxic chemotherapy and radiation and associates with poor prognosis and therapy failure. Targeting therapy against cancer stem cell has emerged as a potential therapeutic approach to develop effective regimens. However, the suitable CSC marker of ESCC for identification and targeting is still limited. In this study, we screened the novel CSC membrane protein markers using two distinct stemness characteristics of cancer cell lines by a comparative approach. After the validation of RT-PCR, qPCR and western blot analyses, intercellular adhesion molecule 1 (ICAM1) was identified as a potential CSC marker of ESCC. ICAM1 promotes cancer cell migration, invasion as well as increasing mesenchymal marker expression and attenuating epithelial marker expression. In addition, ICAM1 contributes to CSC properties, including sphere formation, drug resistance, and tumorigenesis in mouse xenotransplantation model. Based on the analysis of ICAM1-regulated proteins, we speculated that ICAM1 regulates CSC properties partly through an ICAM1-PTTG1IP-p53-DNMT1 pathway. Moreover, we observed that ICAM1 and CD44 could have a compensation effect on maintaining the stemness characteristics of ESCC, suggesting that the combination of multi-targeting therapies should be under serious consideration to acquire a more potent therapeutic effect on CSC of ESCC.
authors.affiliation: Institute of Biochemistry & Molecular Biology, National Yang-Ming University, Taipei, Taiwan.|Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Sheng-Ta
authors.initials: ST
authors.lastname: Tsai
authors.affiliation: Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan.
authors.forename: Po-Jen
authors.initials: PJ
authors.lastname: Wang
authors.affiliation: Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Nia-Jhen
authors.initials: NJ
authors.lastname: Liou
authors.affiliation: Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Pei-Shan
authors.initials: PS
authors.lastname: Lin
authors.affiliation: Institute of Biochemistry & Molecular Biology, National Yang-Ming University, Taipei, Taiwan.|Genomics Research Center, Academia Sinica, Taipei, Taiwan.|Department of Chemistry, National Taiwan University, Taipei, Taiwan.|Institute of Atomic & Molecular Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Chung-Hsuan
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan.|Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Wei-Chao
authors.initials: WC
authors.lastname: Chang
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D055785:Gene Knockdown Techniques; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D040901:Proteomics; D015203:Reproducibility of Results; D015398:Signal Transduction; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018960:Hyaluronan Receptors; D008565:Membrane Proteins; D016159:Tumor Suppressor Protein p53; D018799:Intercellular Adhesion Molecule-1