Krï¿½ppel-like factor 4 negatively regulates β-catenin expression and inhibits the proliferation, invasion and metastasis of gastric cancer

Zhang, Neng; Zhang, Jun; Shuai, L. Y.; Zha, Lang; He, Miao; Huang, Zhen; Wang, Ziwei

doi:10.3892/ijo.2012.1395

Cited by 27 publications

(24 citation statements)

References 47 publications

(67 reference statements)

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“…It has been reported that forced expression of KLF4 in breast tumor cell line and gastric cancer was sufficient to restore E-cadherine expression and inhibit EMT as well as suppressed migration and invasion [56], [60]. In our study, overexpression of KLF4 in spheroid cells led to a significant induction of E-cadherin, Snail as well as vimentin and deduction of ZO-1, the key mediators of EMT (Figure 7B).…”

Section: Discussionsupporting

confidence: 66%

Krüppel-Like Factor 4 Acts as an Oncogene in Colon Cancer Stem Cell-Enriched Spheroid Cells

et al. 2013

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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.

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Section: Discussionsupporting

confidence: 66%

Krüppel-Like Factor 4 Acts as an Oncogene in Colon Cancer Stem Cell-Enriched Spheroid Cells

et al. 2013

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“…In GC, the function of KLF4 has been characterized as tumor suppressor and serves as a prognostic predictor for the survival of patients [18]. Overexpression of KLF4 significantly inhibited gastric cancer cell proliferation, invasion and metastatic properties [19]. This study identified KLF4 as a direct target of miR-103 in GC through dual-luciferase reporter and confirmed by western blot analysis.…”

Section: Discussionmentioning

confidence: 66%

miR-103 Promotes Proliferation and Metastasis by Targeting KLF4 in Gastric Cancer

Zheng

Liu

Qiao

et al. 2017

IJMS

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MicroRNAs (miRNAs) play important roles in the cancer development and progression; overexpression of miR-103 has been identified in various tumors. However, its biological function and regulatory mechanism involved in modulation of human gastric cancer (GC) remain largely unknown. This study aimed to confirm clinical significance of miR-103 and investigate its biological role and underlying mechanism in GC. Real-time quantitative PCR (qRT-PCR) revealed miR-103 was highly expressed in GC tissues and cell lines. miR-103 expression was correlated closely with tumor size, Lauren’s classification, and lymph node metastasis. Importantly, Kaplan-Meier analysis revealed that high expression of miR-103 was significantly associated with poor overall survival and disease-free survival of GC patients. Downregulation of miR-103 by transfecting with miR-103 inhibitor significantly suppressed cell proliferation, induced apoptosis, inhibited migration and invasion in vitro and in vivo. Furthermore, miRNA target databases and luciferase reporter assay confirmed that Krüppel-like Factor-4 (KLF4) was a direct target of miR-103 in GC, and there was a significant inverse correlation between miR-103 and KLF4 expression in GC tissues. Moreover, KLF4 downregulation could rescue miR-103’s oncogenic effect on GC cell proliferation, apoptosis, migration, and invasion. Therefore, these results suggested that miR-103 overexpression could contribute to tumor progression by suppressing KLF4, and it might serve as a promising candidate for the prognosis of GC patients.

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“…KLF4 was shown to undergo promoter methylation and loss of heterozygosity in gastrointestinal cancer (119). Consistent with its tumor-suppressive function, overexpression of KLF4 reduces the tumorigenicity of colonic and gastric cancer cells in vivo (28,125). In colon cancer tissues, KLF4 levels are lower as compared with adjacent noncancer tissues and its expression is inversely correlated with the stage of tumors and survival (126).…”

Section: Roles In Diseasesmentioning

confidence: 86%

Krüppel-like factor 4 (KLF4): What we currently know

Ghaleb

Yang

2017

Gene

442

349

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Krüppel-like factor 4 (KLF4) is an evolutionarily conserved zinc finger-containing transcription factor that regulates diverse cellular processes such as cell growth, proliferation, and differentiation. Since its discovery in 1996, KLF4 has been gaining a lot of attention, after it was shown in 2006 as one of four factors required for the induction of pluripotent stem cells (iPSCs). Here we review the current knowledge on the different functions and roles of KLF4 in various tissue and organ systems.

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Krï¿½ppel-like factor 4 negatively regulates β-catenin expression and inhibits the proliferation, invasion and metastasis of gastric cancer

Cited by 27 publications

References 47 publications

Krüppel-Like Factor 4 Acts as an Oncogene in Colon Cancer Stem Cell-Enriched Spheroid Cells

Krüppel-Like Factor 4 Acts as an Oncogene in Colon Cancer Stem Cell-Enriched Spheroid Cells

miR-103 Promotes Proliferation and Metastasis by Targeting KLF4 in Gastric Cancer

Krüppel-like factor 4 (KLF4): What we currently know

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