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Kruppel-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.

SUBMITTER: Leng Z

PROVIDER: S-EPMC3572033 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Krüppel-like factor 4 acts as an oncogene in colon cancer stem cell-enriched spheroid cells.

Leng Zhengwei Z Tao Kaixiong K Xia Qinghua Q Tan Jun J Yue Zhongyi Z Chen Jinhuang J Xi Hailin H Li Jie J Zheng Hai H

PloS one 20130213 2

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 ...[more]

PMID: 23418515

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Project description:Breast cancer is the second leading cause of cancer-related mortality worldwide as most patients often suffer cancer relapse. The reason is often attributed to the presence of cancer stem cells (CSCs). Recent studies revealed that dysregulation of microRNA (miRNA) are closely linked to breast cancer recurrence and metastasis. However, no specific study has comprehensively characterised the CSC characteristic and miRNA transcriptome in spheroid-enriched breast cells. This study described the generation of spheroid MCF-7 cell in serum-free condition and the comprehensive characterisation for their CSC properties. Subsequently, miRNA expression differences between the spheroid-enriched CSC cells and their parental cells were evaluated using next generation sequencing (NGS). Our results showed that the MCF-7 spheroid cells were enriched with CSCs properties, indicated by the ability to self-renew, increased expression of CSCs markers, and increased resistance to chemotherapeutic drugs. Additionally, spheroid-enriched CSCs possessed greater cell proliferation, migration, invasion, and wound healing ability. A total of 134 significantly (p<0.05) differentially expressed miRNAs were identified between spheroids and parental cells using miRNA-NGS. MiRNA-NGS analysis revealed 25 up-regulated and 109 down-regulated miRNAs which includes some miRNAs previously reported in the regulation of breast CSCs. A number of miRNAs (miR-4492, miR-4532, miR-381, miR-4508, miR-4448, miR-1296, and miR-365a) which have not been previously reported in breast cancer were found to show potential association with breast cancer chemoresistance and self-renewal capability. The gene ontology (GO) analysis showed that the predicted genes were enriched in the regulation of metabolic processes, gene expression, DNA binding, and hormone receptor binding. The corresponding pathway analyses inferred from the GO results were closely related to the function of signalling pathway, self-renewability, chemoresistance, tumorigenesis, cytoskeletal proteins, and metastasis in breast cancer. Based on these results, we proposed that certain miRNAs identified in this study could be used as new potential biomarkers for breast cancer stem cell diagnosis and targeted therapy.

Dataset Information

Kruppel-like factor 4 acts as an oncogene in colon cancer stem cell-enriched spheroid cells.

Publications

Krüppel-like factor 4 acts as an oncogene in colon cancer stem cell-enriched spheroid cells.

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