Knockdown of Oct4 and Nanog expression inhibits the stemness of pancreatic cancer cells

Lu, Yao; Zhu, Hui; Shan, Haiyan; Lu, Junjie; Xu, Chong; Xiao-hong, LI; Lu, Jingjing; Fan, Xiaoxuan; Zhu, Shajun; Wang, Yao; Guo, Qingsong; Wang, Lei; Huang, Yan; Zhu, Mingyan; Wang, Zhiwei

doi:10.1016/j.canlet.2013.07.009

Cited by 135 publications

(121 citation statements)

References 57 publications

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“…In addition, the activation of stem cell-like molecules (CD44, OCT4, KLF4, and ABCG2) was detected in bladder cancer cells overexpressing E2F1, EZH2, and SUZ12. Moreover, the activation of ABCG2 and CD44 could be related to the chemoresistance of the cells and, consequently, enriching CSCs by drug treatment might induce cancer aggressiveness (30,47,48).…”

Section: Discussionmentioning

confidence: 99%

“…S8). Furthermore, mRNA levels of CD44, KLF4, OCT4, and ABCG2 known as CSC markers (29)(30)(31)(32) significantly affected in under MMC-or cisplatin-treated conditions in bladder cancer cells with altered E2F1, EZH2, and SUZ12 expression than in matched control group ( Fig. 6D and Supplementary Fig.…”

Section: Characterization Of Bladder Cancer Cell Lines By Unsupervisementioning

confidence: 95%

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Activation of EZH2 and SUZ12 Regulated by E2F1 Predicts the Disease Progression and Aggressive Characteristics of Bladder Cancer

Lee

Roh

Kim

et al. 2015

Clinical Cancer Research

108

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Purpose: Previous study identified E2F1 as a key mediator of non-muscle-invasive bladder cancer (NMIBC) progression. The aim of this study was to identify the E2F1-related genes associated with poor prognosis and aggressive characteristics of bladder cancer.Experimental Design: Microarray analysis was performed to find E2F1-related genes associated with tumor progression and aggressiveness in the gene expression data from 165 primary patients with bladder cancer. The biologic activity of E2F1-related genes in tumor progression and aggressiveness was confirmed with experimental assays using bladder cancer cells and tumor xenograft assay.Results: The expression of E2F1 was significantly associated with EZH2 and SUZ12. The overexpression of E2F1, EZH2, and SUZ12 enhanced cancer progression including cell colony formation, migration, and invasiveness. Knockdown of these genes reduced motility, blocked invasion, and decreased tumor size in vivo. E2F1 bound the proximal EZH2 and SUZ12 promoter to activate transcription, suggesting that E2F1 and its downstream effectors, EZH2 and SUZ12, could be important mediators for the cancer progression. In addition, we confirmed an association between these genes and aggressive characteristics. Interestingly, the treatment of anticancer drugs to the cells overexpressing E2F1, EZH2, and SUZ12 induced the expression of CD44, KLF4, OCT4, and ABCG2 known as cancer stem cell (CSC)-related genes.Conclusions: The link between E2F1, EZH2, and/or SUZ12 revealed that E2f1 directly regulates transcription of the EZH2 and SUZ12 genes. The signature of E2F1--EZH2--SUZ12 shows a predictive value for prognosis in bladder tumors and the E2F1-EZH2-SUZ12-driven transcriptional events may regulate the cancer aggressiveness and chemo-resistance, which may provide opportunity for development of new treatment modalities. Clin Cancer Res; 21(23); 5391-403. Ó2015 AACR.

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Section: Discussionmentioning

confidence: 99%

Section: Characterization Of Bladder Cancer Cell Lines By Unsupervisementioning

confidence: 95%

Activation of EZH2 and SUZ12 Regulated by E2F1 Predicts the Disease Progression and Aggressive Characteristics of Bladder Cancer

Lee

Roh

Kim

et al. 2015

Clinical Cancer Research

108

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“…Schulz and Hoffmann demonstrated that three genes Oct2, Nanog and Sox2 expressed in embryonic stem cells and testicular cancer cells (40). Recently, researcher showed that human pancreatic cancer tissue express Sox2 (41), Oct4 and Nanog (42). However, the function of Sox2, Oct4 and Nanog in pancreatic cancer cells are ambiguous.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Oct4, Sox2 and Nanog Expression in Pancreatic Cancer Cell Lines and Human Pancreatic Tumor

Assadollahi

Gholami

Zendedel

et al. 2015

Zahedan J Res Med Sci

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Background: Genes are involved in the control of stem cell self-renewal as a new class of molecular markers of cancer. Objectives: In this study, the expression of Oct4, Nanog and Sox2 in cell lines MIA Paca-2, PA-TU-8902 and AsPC-1 and pancreatic cancer tissue were examined. Materials and Methods: In this experimental study, cell lines, MIA Paca-2, PA-TU-8902 and AsPC-1, were cultured in DMEM (Dulbecco's Modified Eagles Medium) and RPMI-1640 (Roswell Park Memorial Institute) containing FBS 10% (fetal bovine serum) in a 37°C incubator containing Co 2 5% and humidity 90%. Samples of tumor and non-cancer pancreatic tumor were purchased Iran tumor bank. Extraction of RNA and synthesis of cDNA was performed. Expression levels of Oct4, Nanog and Sox2 were determined using Real-time PCR. The protein expression levels of target genes in the cell lines were studied by flow cytometry and immunocytochemistry. Results: The expression rate of Oct4, Nanog and Sox2 is more in the cancer cell lines than those in the control (normal tissue) samples. The protein expression levels of target genes in the cell lines were confirmed by flow cytometry and immunocytochemistry. Conclusions:The genes are involved in stem cell self-renewal as a new class of molecular markers of cancer that detected in the pancreatic cell lines. Maybe, these genes play important role in the uncontrolled proliferation of cancer cells.

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“…Expression of these genes is important for the development of tumors, as shown in in vivo experiments. knockdown of Nanog expression inhibits the stemness of pancreatic cancer cells (28). Sox-2 was highly expressed in the clonogenic compartment of pancreatic cancer cells and targeting of Sox-2 could be a worthy strategy for pancreatic cancer therapy (29).…”

Section: Discussionmentioning

confidence: 99%

Combined treatment with tamoxifen and a fusicoccin derivative (ISIR-042) to overcome resistance to therapy and to enhance the antitumor activity of 5-fluorouracil and gemcitabine in pancreatic cancer cells

Miyake¹,

Honma²,

Urano³

et al. 2015

International Journal of Oncology

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Abstract.Although progress has been made in chemotherapeutic strategies against pancreatic cancer, overall survival has not significantly improved over the past decade. Thus, the development of better therapeutic regimens remains a high priority. Pancreatic cancer cell lines were treated with tamoxifen, a novel antitumor fusicoccin derivative (ISIR-042), and anticancer drugs, and their effects on cell growth, signaling and gene expression were determined. Xenografts of Panc-1 cells were treated with tamoxifen, ISIR-042 and 5-fluorouracil (5FU) to determine the effects on tumor growth. The inhibition of the growth of pancreatic cancer cells induced by tamoxifen was effectively reduced by α-tocopherol, a membrane stabilizer. ISIR-042 produced synergistic effects with tamoxifen in inhibiting cell growth. Tamoxifen elevated lipid peroxidation and the release of cytochrome c, and these effects of tamoxifen were reduced by α-tocopherol. ISIR-042 significantly inhibited colony formation and the expression of stemness-related genes of pancreatic cancer cells. The triple combination of tamoxifen, ISIR-042, and 5FU or gemcitabine was effective at inhibiting cell growth and the appearance of drug-resistant cells. This combined treatment significantly inhibited the growth of Panc-1 cells as xenografts without apparent adverse effects. The triple combination of tamoxifen and ISIR-042 with 5FU or gemcitabine may be highly effective against pancreatic cancer by overcoming resistance to therapy.

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Knockdown of Oct4 and Nanog expression inhibits the stemness of pancreatic cancer cells

Cited by 135 publications

References 57 publications

Activation of EZH2 and SUZ12 Regulated by E2F1 Predicts the Disease Progression and Aggressive Characteristics of Bladder Cancer

Activation of EZH2 and SUZ12 Regulated by E2F1 Predicts the Disease Progression and Aggressive Characteristics of Bladder Cancer

Comparison of Oct4, Sox2 and Nanog Expression in Pancreatic Cancer Cell Lines and Human Pancreatic Tumor

Combined treatment with tamoxifen and a fusicoccin derivative (ISIR-042) to overcome resistance to therapy and to enhance the antitumor activity of 5-fluorouracil and gemcitabine in pancreatic cancer cells

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