title: Epigenetic regulation of CD271, a potential cancer stem cell marker associated with chemoresistance and metastatic capacity.
abstract: Cancer stem cells (CSCs) are considered to be the cause of tumor initiation, metastasis and recurrence. Additionally, CSCs are responsible for the failure of chemotherapy and radiotherapy. The isolation and identification of CSCs is crucial for facilitating the monitoring, therapy or prevention of cancer. We aimed to identify esophageal squamous cell carcinoma (ESCC) stem-like cells, the epigenetic mechanism and identify novel biomarkers for targeting ESCC CSCs. Sixty-three paired ESCC tissues and adjacent non-cancerous tissues were included in this study. CD271, which was identified as the CSC marker for melanoma, was assessed using quantitative PCR (qPCR). Using flow cytometry, we isolated CD271+ cells comprising 7.5% of cancer cells from the KYSE70 cell line. Sphere formation and anchorage-independent growth were analyzed in CD271+ and CD271- cancer cells, respectively. qPCR was used to detect stem-related genes and CCK-8 was performed to analyze the sensitivity to chemotherapy in the two groups. Bisulﬁte genomic sequencing was used to analyze the methylation status. CD271 expression was significantly higher in ESCC tissues than in adjacent non-cancerous tissues. Compared with CD271- cancer cells, CD271+ cancer cells showed a higher ability of sphere and colony formation, a high level expression of stem-related gene, and resistance to chemotherapy. The expression of CD271 was induced by a demethylation agent. In conclusion, CD271+ ESCC cells possess stem-like properties. CD271 can potentially act as a prognostic marker for ESCC, whose expression is regulated epigenetically.
authors.affiliation: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Sulan
authors.initials: S
authors.lastname: Li
authors.affiliation: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Dongli
authors.initials: D
authors.lastname: Yue
authors.affiliation: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Jieyao
authors.initials: J
authors.lastname: Li
authors.affiliation: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ping
authors.affiliation: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.affiliation: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019175:DNA Methylation; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D044127:Epigenesis, Genetic; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; C486780:NANOG protein, human; C484065:NGFR protein, human; D000071317:Nanog Homeobox Protein; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; D002945:Cisplatin; D005472:Fluorouracil