Decreased CDK10 expression correlates with lymph node metastasis and predicts poor outcome in breast cancer patients - a short report

You, Yanjie; Li, Haijun; Xin, Qin; Zhang, Yinpo; Song, Wengang; Ran, Yonggang; Gao, Fenglan

doi:10.1007/s13402-015-0246-4

Cited by 22 publications

(29 citation statements)

References 31 publications

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“…It has been demonstrated that CDK10 expression is downregulated in nasopharyngeal carcinoma, and that overexpression of CDK10 strongly suppresses the growth and metastasis of cancer cells (10), which is consistent with studies on hepatocellular carcinoma and biliary tract cancer (11,12). More recent reports revealed that CDK10 expression levels were decreased in breast cancer, and that CDK10 expression was significantly associated with lymph node metastasis and unfavorable patient survival (13,14). These data indicated that CDK10 may serve as a tumor suppressor and that silencing of CDK10 may contribute to metastatic progression; however, the precise underlying molecular mechanism is largely unknown.…”

Section: Introductionsupporting

confidence: 82%

Cyclin‑dependent kinase 10 prevents glioma metastasis via modulation of Snail expression

You

Liu

2018

Mol Med Report

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Cyclin‑dependent kinase 10 (CDK10) has been indicated to be a candidate tumor suppressor in multiple cancer types. However, to the best of the authors' knowledge, its biological and regulatory functions in glioma have not been previously reported. In the present study, it was demonstrated that overexpression of CDK10 inhibited glioma cell proliferation and metastasis. By contrast, knockdown of CDK10 expression promoted these malignant phenotypes. It was additionally indicated that dysregulated CDK10 expression was associated with epithelial‑mesenchymal transition (EMT) and that it regulated the expression of zinc finger protein SNAI1 (Snail). Furthermore, silencing Snail expression rescued EMT phenotypes induced by CDK10 knockdown, suggesting that Snail may be involved in the mechanistic association between CDK10 and EMT. The present study illustrated that downregulation of CDK10 expression activated Snail‑driven EMT and consequently promoted glioma metastasis, suggesting that CDK10 may serve as a potential molecular target for glioma therapy.

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Section: Introductionsupporting

confidence: 82%

Cyclin‑dependent kinase 10 prevents glioma metastasis via modulation of Snail expression

You

Liu

2018

Mol Med Report

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“…Although a recent study argued that CDK10 is a candidate therapeutic target for colorectal adenocarcinomas (Weiswald et al, 2017), a number of reports indicate that CDK10 acts as a tumor suppressor in various cancers of the digestive system, including biliary tract cancer , hepatocellular carcinomas , gastric carcinomas (Zhao et al, 2017;You et al, 2018), and in nasopharyngeal carcinomas (You et al, 2013), gliomas (Li et al, 2018) and advanced breast cancers (You et al, 2015). These contradictory findings could be explained by the fact that ETS2, whose stability is controlled in part by CDK10/CycM phosphorylation (Guen et al, 2013), can function either as an oncogene or a tumor suppressor depending on various factors such as cellular context and p53 status (Martinez, 2016).…”

Section: Discussionmentioning

confidence: 99%

Development of a CDK10/CycM in vitro Kinase Screening Assay and Identification of First Small-Molecule Inhibitors

et al. 2020

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Cyclin-dependent kinases (CDKs) constitute a family of 20 serine/threonine protein kinases that play pivotal roles in the regulation of numerous important molecular and cellular processes. CDKs have long been considered promising therapeutic targets in a variety of pathologies, and the recent therapeutic success of CDK4/6 inhibitors in breast cancers has renewed interest in their therapeutic potential. Small-molecule inhibitors have been identified for every human CDK, except for CDK10. The only recent discovery of an activating cyclin (CycM) for CDK10 enabled us to identify its first phosphorylation substrates and gain insights into its biological functions. Yet, our knowledge of this kinase remains incomplete, despite it being the only member of its family that causes severe human developmental syndromes, when mutated either on the cyclin or the CDK moiety. CDK10 small-molecule inhibitors would be useful in exploring the functions of this kinase and gauging its potential as a therapeutic target for some cancers. Here, we report the identification of an optimized peptide phosphorylation substrate of CDK10/CycM and the development of the first homogeneous, miniaturized CDK10/CycM in vitro kinase assay. We reveal the ability of known CDK inhibitors, among which clinically tested SNS-032, riviciclib, flavopiridol, dinaciclib, AZD4573 and AT7519, to potently inhibit CDK10/CycM. We also show that NVP-2, a strong, remarkably selective CDK9 inhibitor is an equally potent CDK10/CycM inhibitor. Finally, we validate this kinase assay for applications in high-throughput screening campaigns to discover new, original CDK10 inhibitors.

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“…Western blot analysis. This procedure was performed as described previously (18)(19)(20)(21). Frozen tissue samples, including gastric cancer tissues and paired adjacent non-cancerous tissues obtained from 12 patients were prepared in radioimmunoprecipitation assay lysis buffer (Beyotime Institute of Biotechnology).…”

Section: Patient Information and Tissue Specimens A Microarray Chip mentioning

confidence: 99%

“…Immunohistochemical analysis was performed as described previously (20,21). Sections (4 µm thick) were cut from tissue specimens fixed in 10% buffered formalin and embedded in paraffin.…”

Section: Immunohistochemistry and Evaluationmentioning

confidence: 99%

Decreased ST2 expression is associated with gastric cancer progression and pathogenesis

Bai

You

et al. 2019

Oncol Lett

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Gastric cancer is a type of cancer with increasing incidence and high mortality rates, but molecular biomarkers of diagnostic and therapeutic value are currently lacking. The aim of the present study was to examine the expression pattern of the interleukin 1 receptor-like 1 (ST2) protein and assess its clinicopathological significance in gastric cancer. Western blot analysis of 12 gastric cancer specimens and paired adjacent tissues demonstrated that the protein levels of 2 isoforms of ST2, soluble secreted ST2 and the ST2 variant without the third immunoglobulin motif and splicing in the C-terminal, were markedly decreased in cancer tissues compared with non-cancerous tissues. Immunohistochemical analysis demonstrated that ST2 protein expression was markedly decreased in primary gastric cancer tissues (39.1%, 90/230) compared with adjacent non-cancerous tissues (60.7%, 54/89) (P<0.05). Statistical analysis demonstrated that decreased ST2 expression was significantly associated with advanced tumor node metastasis stage (P<0.001) and tumor differentiation (P<0.001). These data suggest that ST2 protein may be a valuable biomarker of gastric cancer progression and pathogenesis.

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Decreased CDK10 expression correlates with lymph node metastasis and predicts poor outcome in breast cancer patients - a short report

Abstract: Down-regulated CDK10 expression frequently occurs in breast cancers and correlates with disease progression and poor survival. CDK10 may serve as a prognostic biomarker for breast cancer.

Cited by 22 publications

References 31 publications

Cyclin‑dependent kinase 10 prevents glioma metastasis via modulation of Snail expression

Cyclin‑dependent kinase 10 prevents glioma metastasis via modulation of Snail expression

Development of a CDK10/CycM in vitro Kinase Screening Assay and Identification of First Small-Molecule Inhibitors

Decreased ST2 expression is associated with gastric cancer progression and pathogenesis

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