Cyclin-dependent kinases

Kim

Food Science & Nutrition

2018

Orostachys japonicus (O. japonicus) is utilized as a traditional medicine for patients with various diseases. This study investigated the effect of the ethyl acetate fraction from O. japonicus extract (OJE) on the growth inhibition of OVCAR‐3 human ovarian cancer cells demonstrated to inhibit cell growth and arrest the cell cycle in OVCAR‐3 cells by blocking the sub‐G1 phase and decreasing cyclin E1/CDK2 expression. Cell cycle arrest was connected to the increased expression of the cell cycle regulating factors p53 and p21. Apoptosis was initiated through the intrinsic pathway by up‐regulating the expression of the Bcl‐2/Bax ratio and down‐regulating the expression of pro‐caspase‐3. Furthermore, OJE treatment elicited p‐p38 activation and p‐ERK1/2 inhibition. In conclusion, our results demonstrated that OJE reduced the growth of OVCAR‐3 human ovarian cancer cells mediated by arrest of the cell cycle and regulation of MAPK signaling pathways.

Section: Resultsmentioning

confidence: 99%

Orostachys japonicus induce p53‐dependent cell cycle arrest through the MAPK signaling pathway in OVCAR‐3 human ovarian cancer cells

Kim

Food Science & Nutrition

2018

“…1 Deregulation of CDKs is directly linked to oncogenesis. CDKs are reliant on binding a cyclin for their activation.…”

Section: Introductionmentioning

confidence: 99%

“…To date, at least 20 CDKs and 30 cyclins have been reported. 1,2 Among them, CDK1, CDK2, CDK4 and CDK6 regulate the transition of phases in the cell cycle while CDKs 7-11 are involved in transcription. 3 CDK6 gene is located in human chromosome 7 and is translated into a kinase with 326 amino acids.…”

Section: Introductionmentioning

confidence: 99%

Targeting CDK6 in cancer: State of the art and new insights

et al. 2015

Cyclin-dependent kinase 6 (CDK6) plays a vital role in regulating the progression of the cell cycle. More recently, CDK6 has also been shown to have a transcriptional role in tumor angiogenesis. Up-regulated CDK6 activity is associated with the development of several types of cancers. While CDK6 is over-expressed in cancer cells, it has a low detectable level in non-cancerous cells and CDK6-null mice develop normally, suggesting a specific oncogenic role of CDK6, and that its inhibition may represent an ideal mechanism-based and low toxic therapeutic strategy in cancer treatment. Identification of selective small molecule inhibitors of CDK6 is thus needed for drug development. Herein, we review the latest understandings of the biological regulation and oncogenic roles of CDK6. The potential clinical relevance of CDK6 inhibition, the progress in the development of small-molecule CDK6 inhibitors and the rational design of potential selective CDK6 inhibitors are also discussed.

“…Therefore, an increase in the proportion of cells at S and G2/M phase represented an enhanced proliferation of cells 22. Cyclin‐dependent kinases (CDKs), such as CDK4 and CDK6, were a family of protein kinases that were first discovered for their role in regulating the cell cycle 23, 24. Cyclin D1 forms protein complex with CDK4 or CDK6, the activity of which is necessary for cell cycle G1/S transition 25.…”

Section: Discussionmentioning

confidence: 99%

Upregulated IQUB promotes cell proliferation and migration via activating Akt/GSK3β/β‐catenin signaling pathway in breast cancer

Zhang

et al. 2018

Cancer Medicine

Breast cancer was the highest incidence of tumor in women, which seriously threaten women's health. Our previous study found that the expression of IQUB (IQ motif and ubiquitin domain containing) was significantly increased in the development of breast cancer by transcriptome sequencing. However, there were no studies on the mechanism of IQUB in tumorigenesis. Further study showed that IQUB expression was significantly increased in breast cancer, which had a significantly positive correlation with pathological differentiation of breast cancer by tissue microarray analysis. Furthermore, we also discovered that IQUB overexpression could obviously promote the proliferation and migration of MCF‐7 cells and increase the proportion of MCF‐7 cells in S and G2/M phase in vitro study, while knockdown of IQUB caused inhibition of cell proliferation and migration in MDA‐MB‐231 cells and increased the proportion of MDA‐MB‐231 cells in G1 phase. Furthermore, IQUB overexpression or knockdown combined with treatment of Licl or MG‐132 showed that IQUB activated Akt to promote GSK3β phosphorylation, which in turn activated Wnt/β‐catenin signaling pathway in breast cancer cells. Taken together, these results indicated that upregulated IQUB promoted breast cancer cell proliferation and migration via activating Akt/GSK3β/β‐catenin signaling pathway, which played an important part in the tumorigenesis and development of breast cancer.