KLF5-mediated COX2 upregulation contributes to tumorigenesis driven by PTEN deficiency

Zhang, Liang; Wu, Yuncui; Wu, Jing; Zhou, Meng; Li, Dapeng; Wan, Xiaofeng; Jin, Fuquan; Wang, Yani; Lin, Wei; Zha, Xiaojun; Liu, Yehai

doi:10.1016/j.cellsig.2020.109767

Cited by 7 publications

(7 citation statements)

References 38 publications

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“…Mycoplasma test was performed using TaKaRa PCR Mycoplasma Detection Set (Clontech Laboratories, EUA), before all experiments. For in vitro assays, the drug concentration was chosen as suggested by the manufacturer's protocols or according to previous studies [16][17][18][19][20] . Clinical samples of invasive breast cancer and their paired normal tissues (adjacent normal tissues) were obtained from patients undergoing surgical resection in the Department of Breast Surgery, the First Affiliated Hospital of Anhui Medical University from March 2017 to June 2019.…”

Section: Cell Cultures and Clinical Tissue Samplesmentioning

confidence: 99%

AKT1-CREB stimulation of PDGFRα expression is pivotal for PTEN deficient tumor development

et al. 2021

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As evidenced by the behavior of loss-of-function mutants of PTEN in the context of a gain-of-function mutation of AKT1, the PTEN-AKT1 signaling pathway plays a critical role in human cancers. In this study, we demonstrated that a deficiency in PTEN or activation of AKT1 potentiated the expression of platelet-derived growth factor receptor α (PDGFRα) based on studies on Pten−/− mouse embryonic fibroblasts, human cancer cell lines, the hepatic tissues of Pten conditional knockout mice, and human cancer tissues. Loss of PTEN enhanced PDGFRα expression via activation of the AKT1-CREB signaling cascade. CREB transactivated PDGFRα expression by direct binding of the promoter of the PDGFRα gene. Depletion of PDGFRα attenuated the tumorigenicity of Pten-null cells in nude mice. Moreover, the PI3K-AKT signaling pathway has been shown to positively correlate with PDGFRα expression in multiple cancers. Augmented PDGFRα was associated with poor survival of cancer patients. Lastly, combination treatment with the AKT inhibitor MK-2206 and the PDGFR inhibitor CP-673451 displayed synergistic anti-tumor effects. Therefore, activation of the AKT1-CREB-PDGFRα signaling pathway contributes to the tumor growth induced by PTEN deficiency and should be targeted for cancer treatment.

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Section: Cell Cultures and Clinical Tissue Samplesmentioning

confidence: 99%

AKT1-CREB stimulation of PDGFRα expression is pivotal for PTEN deficient tumor development

et al. 2021

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“…Ma et al [29] showed that KLF5 reduced STAT3 activity and tumor metastasis in prostate cancer. Sun et al [30] reported that liver cancer cells with KLF5 knockdown displays a sharp and round shape and promotes mesenchymal-to-epithelial transition. Our experiments demonstrated that KLF5 is the target of miR-204 and functional assays revealed that KLF5 overexpression promoted PTC cell viability and invasion of PTC.…”

Section: Discussionmentioning

confidence: 99%

Fentanyl Exerts an Antitumor Effect on Papillary Thyroid Cancer by Regulating the miR-204/KLF5 Axis

Jiang

Dai

et al. 2021

Journal of Nanomaterials

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Fentanyl is a strong anesthetic analgesic drug that plays important roles in many types of cancers. However, the role of fentanyl in papillary thyroid cancer (PTC) tumor development remains ambiguous. In this study, we aimed to investigate the potential antitumor effects of fentanyl on PTC cell viability and invasion. Results of cell counting kit-8 and Transwell assays demonstrated that fentanyl treatment (5 ng/ml) reduced the viability and invasion of two PTC cells, TCP-1 and BCPAP. Our data subsequently showed that fentanyl induced antitumor effects by increasing miR-204 expressions. Furthermore, the results of luciferase reporter assays identified that miR-204 directly targets Krüppel-like transcription factor 5 (KLF5), which serves as tumor-promoting genes in many cancers. Further mechanistic analyses revealed that fentanyl performs its tumor-suppressive functions by regulating the miR-204/KLF5 axis in PTC cells. These results contribute to understanding the important role of fentanyl in treating PTC.

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“…4 In addition to mPGES1, KLF5 was reported to induce cyclooxygenase 2 (COX2) expression and promote cell proliferation and migration in phosphate and tension homology deleted on chromosome ten (PTEN)-null mouse embryonic fibroblasts. 28 Consistently, KLF5 also promotes the transcription of Cyclin E1 by binding to its polymorphic enhancer in bladder cancer. 29 KLF5 was reported to promote bladder cancer cell migration by promoting the transcription of the FYN proto-oncogene kinase (FYN) gene, which thereby activates FAK.…”

Section: Tr An Scrip Ti Onal Targ E T G Ene Smentioning

confidence: 93%

“…Accumulating evidence from our laboratory has suggested that KLF5 promotes breast cancer by regulating several key target genes, including FGF‐BP1 , 25 microsomal prostaglandin E‐2 synthase 1 ( mPGES1 ), 26 tumor necrosis factor‐α ( TNFα ) ‐induced protein 2 ( TNFAIP2 ), 27 Slug , 7 and Cyclin D1 4 . In addition to mPGES1 , KLF5 was reported to induce cyclooxygenase 2 (COX2) expression and promote cell proliferation and migration in phosphate and tension homology deleted on chromosome ten (PTEN)‐null mouse embryonic fibroblasts 28 . Consistently, KLF5 also promotes the transcription of Cyclin E1 by binding to its polymorphic enhancer in bladder cancer 29 .…”

Section: Transcriptional Target Genesmentioning

confidence: 99%

The roles and regulation of the KLF5 transcription factor in cancers

Luo

Chen

2021

Cancer Science

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KLF5-mediated COX2 upregulation contributes to tumorigenesis driven by PTEN deficiency

Cited by 7 publications

References 38 publications

AKT1-CREB stimulation of PDGFRα expression is pivotal for PTEN deficient tumor development

AKT1-CREB stimulation of PDGFRα expression is pivotal for PTEN deficient tumor development

Fentanyl Exerts an Antitumor Effect on Papillary Thyroid Cancer by Regulating the miR-204/KLF5 Axis

The roles and regulation of the KLF5 transcription factor in cancers

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