CDK8 regulates the angiogenesis of pancreatic cancer cells in part via the CDK8-β-catenin-KLF2 signal axis

Wei, Ran; Kong, Ling-Dong; Xiao, Yuhong; Yuan, Huiping; Song, Yi; Wang, Jia; Yu, Huihuan; Mao, Shengxun; Xu, Wei

doi:10.1016/j.yexcr.2018.05.033

Cited by 24 publications

(17 citation statements)

References 68 publications

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“…Follow-up studies in patients with colorectal cancer demonstrated that upregulation of Cdk8 led to decreased survival [100]. More recently, angiogenesis in a pancreatic cancer model was enhanced by Cdk8 activation of the β-catenin-Krüppel-like factor 2 (KLF2) signaling axis [101]. In addition, Cdk8 has been shown to activate the oncogene YAP through direct phosphorylation, leading to colon cancer tumorigenesis [102].…”

Section: Cyclin C-cdk8 As An Oncogenementioning

confidence: 99%

Cyclin C: The Story of a Non-Cycling Cyclin

Ježek

Smethurst

Stieg

et al. 2019

Biology

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The class I cyclin family is a well-studied group of structurally conserved proteins that interact with their associated cyclin-dependent kinases (Cdks) to regulate different stages of cell cycle progression depending on their oscillating expression levels. However, the role of class II cyclins, which primarily act as transcription factors and whose expression remains constant throughout the cell cycle, is less well understood. As a classic example of a transcriptional cyclin, cyclin C forms a regulatory sub-complex with its partner kinase Cdk8 and two accessory subunits Med12 and Med13 called the Cdk8-dependent kinase module (CKM). The CKM reversibly associates with the multi-subunit transcriptional coactivator complex, the Mediator, to modulate RNA polymerase II-dependent transcription. Apart from its transcriptional regulatory function, recent research has revealed a novel signaling role for cyclin C at the mitochondria. Upon oxidative stress, cyclin C leaves the nucleus and directly activates the guanosine 5’-triphosphatase (GTPase) Drp1, or Dnm1 in yeast, to induce mitochondrial fragmentation. Importantly, cyclin C-induced mitochondrial fission was found to increase sensitivity of both mammalian and yeast cells to apoptosis. Here, we review and discuss the biology of cyclin C, focusing mainly on its transcriptional and non-transcriptional roles in tumor promotion or suppression.

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Section: Cyclin C-cdk8 As An Oncogenementioning

confidence: 99%

Cyclin C: The Story of a Non-Cycling Cyclin

Ježek

Smethurst

Stieg

et al. 2019

Biology

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“…The data indicate that the combination might simultaneously target CDKs and Akt/mTOR signalling to inhibit both tumour progress and angiogenesis [ 207 ]. Angiogenesis is further influenced by CDK8, which has been found that when overexpressed, it promotes angiogenesis in pancreatic cancer via activation of CDK8/β-catenin/KLF2 signalling, while silencing of CDK8 inhibits angiogenesis in pancreatic cancer in vitro and in nude mice xenograft models [ 208 ]. However, the transfer of these hopeful preclinical models to the clinic, where vast genetic tumour heterogeneity and, consequently, dynamics of tumour growth are highly inconsistent between patients, is extremely challenging [ 209 , 210 ].…”

Section: Cdk Inhibition In Pdacmentioning

confidence: 99%

The Emerging Role of Cyclin-Dependent Kinases (CDKs) in Pancreatic Ductal Adenocarcinoma

García-Reyes

Kretz

Ruff

et al. 2018

IJMS

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The family of cyclin-dependent kinases (CDKs) has critical functions in cell cycle regulation and controlling of transcriptional elongation. Moreover, dysregulated CDKs have been linked to cancer initiation and progression. Pharmacological CDK inhibition has recently emerged as a novel and promising approach in cancer therapy. This idea is of particular interest to combat pancreatic ductal adenocarcinoma (PDAC), a cancer entity with a dismal prognosis which is owed mainly to PDAC’s resistance to conventional therapies. Here, we review the current knowledge of CDK biology, its role in cancer and the therapeutic potential to target CDKs as a novel treatment strategy for PDAC.

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“…Cyclin-dependent kinase8 ( CDK8 ) belongs to the CDK family, and the members of this protein family influence a variety of biological behaviors, such as angiogenesis, stem cell self-renewal and sperm formation. 14 Emerging studies indicated that CDK8 was overexpressed and accelerated the progression of tumor cells in multiple cancers, such as colon cancer, 15 pancreatic cancer 16 and glioma. 17 Importantly, Li et al found that CDK8 was associated with sensitivity of PTX in NCI60 cells.…”

Section: Introductionmentioning

confidence: 99%

<p>Circ_0006528 Contributes to Paclitaxel Resistance of Breast Cancer Cells by Regulating miR-1299/CDK8 Axis</p>

Liu

Zhang

et al. 2020

OTT

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Background: Circular RNAs (circRNAs) have been reported to be involved in regulating the development of breast cancer. Paclitaxel (PTX) can be used for the chemotherapy of breast cancer. The study aimed to explore the role and mechanism of circ_0006528 in PTXresistant breast cancer progression. Methods: The levels of circ_0006528, microRNA-1299 (miR-1299) and cyclin-dependent kinase 8 (CDK8) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). RNase R treatment was used to confirm that the circ_0006528 was a circular RNA. PTX resistance and cell proliferation were determined by Cell counting kit-8 (CCK-8) assay. Cell apoptosis, migration and invasion were analyzed by flow cytometry and Transwell assays, respectively. The levels of all proteins were examined by Western blot. The interaction between circ_0006528 and miR-1299 or CDK8 was predicted by online database confirmed by dualluciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft mice model was constructed to reveal the role of circ_0006528 on tumor growth in vivo. Results: Circ_0006528 was significantly up-regulated and miR-1299 was down-regulated in PTX-resistant breast cancer tissues and cells compared with control groups. CDK8 protein expression was dramatically upregulated in PTX-resistant breast cancer tissues and cells as compared to control groups. Loss-of-function experiments revealed that circ_0006528 knockdown decreased IC50 value of PTX and restrained proliferation, migration, invasion and autophagy, whereas induced apoptosis of PTX-resistant breast cancer cells in vitro. The inhibitory effects of sh-circ_0006528 on the progression of PTX-resistant breast cancer cells were reversed by decreasing miR-1299 or increasing CDK8 expression. Furthermore, circ_0006528 could modulate CDK8 expression by sponging miR-1299. Circ_0006528 silencing impeded the growth of PTX-resistant tumors by regulating miR-1299/CDK8 axis in vivo. Conclusion: Circ_0006528 partially contributed to PTX resistance of breast cancer cells through up-regulating CDK8 expression by sponging miR-1299.

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CDK8 regulates the angiogenesis of pancreatic cancer cells in part via the CDK8-β-catenin-KLF2 signal axis

Cited by 24 publications

References 68 publications

Cyclin C: The Story of a Non-Cycling Cyclin

Cyclin C: The Story of a Non-Cycling Cyclin

The Emerging Role of Cyclin-Dependent Kinases (CDKs) in Pancreatic Ductal Adenocarcinoma

<p>Circ_0006528 Contributes to Paclitaxel Resistance of Breast Cancer Cells by Regulating miR-1299/CDK8 Axis</p>

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