ABSTRACT
BACKGROUND: CDK8 is associated with the transcriptional Mediator complex and has been shown to regulate several transcription factors implicated in cancer. As a pancreatic cancer oncogene, the role of CDK8 in cancer angiogenesis remains unclear. Here, we investigated the contribution of CDK8 in pancreatic cancer angiogenesis and examined the underlying molecular mechanisms. METHODS: CDK8 expression was evaluated via immunohistochemistry, western blotting, and qRT-PCR in relation to the clinicopathological characteristics of pancreatic cancer patients. The effects of silencing or overexpressing CDK8 on cancer angiogenesis were assessed in vitro by western blotting assays in pancreatic cancer cell lines and in vivo with nude mice xenograft models. RESULTS: Compared with adjacent normal tissues, pancreatic cancer tissues showed upregulation of CDK8 expression, which was inversely correlated with T grade, liver metastasis, size, lymph node metastasis and poor survival. CDK8 overexpression promoted angiogenesis in pancreatic cancer via activation of the CDK8-ß-catenin-KLF2 signaling axis, as demonstrated by the upregulation and downregulation of signals representing the rate-limiting steps in angiogenesis. Silencing CDK8 inhibited angiogenesis in pancreatic cancer in vitro. Additionally, these results were confirmed in nude mice xenograft models in vivo. CONCLUSIONS: CDK8 promotes angiogenesis in pancreatic cancer via activation of the CDK8-ß-catenin-KLF2 signaling axis, thus providing valid targets for the treatment of pancreatic cancer.
Subject(s)
Cyclin-Dependent Kinase 8/metabolism , Kruppel-Like Transcription Factors/metabolism , Neovascularization, Pathologic/metabolism , Pancreatic Neoplasms/blood supply , Pancreatic Neoplasms/metabolism , beta Catenin/metabolism , Aged , Animals , Cell Line, Tumor , Cyclin-Dependent Kinase 8/antagonists & inhibitors , Cyclin-Dependent Kinase 8/genetics , Female , Gene Knockdown Techniques , Heterografts , Humans , Kruppel-Like Transcription Factors/antagonists & inhibitors , Kruppel-Like Transcription Factors/genetics , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Middle Aged , Neovascularization, Pathologic/genetics , Pancreatic Neoplasms/genetics , RNA, Small Interfering/genetics , Signal Transduction , Up-Regulation , beta Catenin/antagonists & inhibitors , beta Catenin/geneticsABSTRACT
The human rhomboid family-1 gene (RHBDF1) is an oncogene in breast and head and neck squamous cancers. Here, we show that RHBDF1 plays a significant role in colorectal cancer (CRC) formation and that the RHBDF1 expression level is higher in CRC than in corresponding normal tissues. Moreover, RHBDF1 promotes cell proliferation, invasion and migration in vitro. Furthermore, through overexpression and silencing of RHBDF1 and the mediator complex, our study demonstrates that RHBDF1 may positively regulate adenomatous polyposis coli (APC) in the Wnt/ß-catenin signalling pathway to increase the expression levels of MMP-14 and Twist, which act as important epithelial-to-mesenchymal transition (EMT) stimulating factors. Additionally, RHBDF1 may regulate c-myc and CyclinD1 expression to influence cell proliferation. Finally, RHBDF1 overexpression and silencing influence CRC growth in BALB/c nude mice. In summary, our findings demonstrate that the regulatory effects of RHBDF1 on EMT and on cell proliferation are partially attributable to the Wnt/ß-catenin signalling pathway.
Subject(s)
Adenomatous Polyposis Coli/metabolism , Gene Expression Regulation, Neoplastic , Membrane Proteins/metabolism , Wnt Signaling Pathway/physiology , Animals , Cell Line, Tumor , Cell Movement/physiology , Cell Proliferation/physiology , Cell Transformation, Neoplastic/metabolism , Epithelial-Mesenchymal Transition/physiology , Humans , Mice, Inbred BALB C , Mice, Nude , beta Catenin/metabolismABSTRACT
Dependences of gas-barrier performance on the deposition temperature of atomic-layer-deposited (ALD) Al2O3, HfO2, and ZnO films were studied to establish low-temperature ALD processes for encapsulating organic light-emitting diodes (OLEDs). By identifying and controlling the key factors, i.e. using H2O2 as an oxidant, laminating Al2O3 with HfO2 or ZnO layers into AHO or AZO nanolaminates, and extending purge steps, OLED-acceptable gas-barrier performance (water vapor transmission rates â¼ 10-6 g m-2 d-1) was achieved for the first time at a low deposition temperature of 50 °C in a thermal ALD mode. The compatibility of the low-temperature ALD process with OLEDs was confirmed by applying the process to encapsulate different types of OLED devices, which were degradation-free upon encapsulation and showed adequate lifetime during accelerated aging tests (pixel shrinkage <5% after 240 h at 60 °C/90% RH).