title: Krüppel-like factor 4 acts as an oncogene in colon cancer stem cell-enriched spheroid cells.
abstract: Cancer stem cells (CSCs), a rare population in any type of cancers, including colon cancer, are tumorigenic. It has been thought that CSCs are responsible for cancer recurrence, metastasis, and drug resistance. Isolating CSCs in colon cancers is challenging, and thus the molecular mechanism regulating the self-renewing and differentiation of CSCs remains unknown. We cultured DLD-1 cells, one of types of cells derived from colon cancers, in serum-free medium to obtain spheroid cells. These cells possessed the characteristics of CSCs, with the expression of CD133, CD166, Lgr5, and ALDH1, higher capacities of chemo-resistance, migration, invasion, and tumorigenicity in vitro and in vivo than the adherent DLD-1 cells. Krüppel-like factor 4 (KLF4) is essential factor for maintaining self-renewal of adult and embryonic stem cells. It has been used to induce pluripotent stem cells (iPS) from somatic cells. Since KLF4 is expressed in colon cancer cells, we investigated its role in spheroid cells isolated from DLD-1 cells and found that KLF4 was overexpressed only in spheroid cells and reducing the expression of KLF4 by short-hairpin RNA significantly decreased the capacities of these cells to resist the chemicals, migrate, invade, and generate tumors in vitro and in vivo. The spheroid cells with reduced KLF4 expression also had decreased expression of CSCs markers and mesenchymal markers. Taken together, culturing DLD-1 cells in serum-free medium enriches CSCs and the expression of KLF4 is essential for the characteristics of CSCs in DLD-1; thus KLF4 can be a potential therapeutic target for treating colon cancer.
authors: Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors: Zhengwei
authors: Z
authors: Leng
authors: Kaixiong
authors: K
authors: Tao
authors: Qinghua
authors: Q
authors: Xia
authors: Jun
authors: J
authors: Tan
authors: Zhongyi
authors: Z
authors: Yue
authors: Jinhuang
authors: J
authors: Chen
authors: Hailin
authors: H
authors: Xi
authors: Jie
authors: J
authors: Li
authors: Hai
authors: H
authors: Zheng
mesh_terms: D000071916:AC133 Antigen; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D005260:Female; D005326:Fetal Proteins / Q000235:genetics / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D015513:Oncogene Proteins / Q000235:genetics*; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018874:Spheroids, Cellular / Q000378:metabolism* / Q000473:pathology; D014183:Transplantation, Heterologous; D020410:Activated-Leukocyte Cell Adhesion Molecule
chemical_list: D000071916:AC133 Antigen; D000080924:Aldehyde Dehydrogenase 1 Family; D015703:Antigens, CD; D015816:Cell Adhesion Molecules, Neuronal; D005326:Fetal Proteins; D006023:Glycoproteins; D007527:Isoenzymes; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D015513:Oncogene Proteins; D010455:Peptides; D043562:Receptors, G-Protein-Coupled; D050697:Retinal Dehydrogenase; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; C116884:LGR5 protein, human; C000606023:PROM1 protein, human; C000606024:Prom1 protein, mouse; C510223:ALDH1A1 protein, human; C515028:ALDH1A1 protein, mouse