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Anti-tumor effect of CDK inhibitors on CDKN2A-defective squamous cell lung cancer cells

Overview of attention for article published in Cellular Oncology (2211-3428), September 2018
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Title
Anti-tumor effect of CDK inhibitors on CDKN2A-defective squamous cell lung cancer cells
Published in
Cellular Oncology (2211-3428), September 2018
DOI 10.1007/s13402-018-0404-6
Pubmed ID
Authors

Eun-Hui Jeong, Tae-Gul Lee, Yun Jung Ko, Seo Yun Kim, Hye-Ryoun Kim, Hyunggee Kim, Cheol Hyeon Kim

Abstract

Squamous cell lung cancer (SqCLC) is a distinct histologic subtype of non-small cell lung cancer (NSCLC). Although the discovery of driver mutations and their targeted drugs has remarkably improved the treatment outcomes for lung adenocarcinoma, currently no such molecular target is clinically available for SqCLC. The CDKN2A locus at 9p21 encodes two alternatively spliced proteins, p16INK4a (p16) and p14ARF (p14), which function as cell cycle inhibitors. The Cancer Genome Atlas (TCGA) project revealed that CDKN2A is inactivated in 72% of SqCLC cases. In addition, it was found that CDKN2A mutations are significantly more common in SqCLC than in adenocarcinoma. Down-regulation of p16 and p14 by CDKN2A gene inactivation leads to activation of cyclin-dependent kinases (CDKs), thereby permitting constitutive phosphorylation of Rb and subsequent cell cycle progression. Here, we hypothesized that CDK inhibition may serve as an attractive strategy for the treatment of CDKN2A-defective SqCLC. We investigated whether the CDK inhibitors flavopiridol and dinaciclib may exhibit antitumor activity in CDKN2A-defective SqCLC cells compared to control cells. The cytotoxic effect of the CDK inhibitors was evaluated using cell viability assays, and the induction of apoptosis was assessed using TUNEL assays and Western blot analyses. Finally, anti-tumor effects of the CDK inhibitors on xenografted cells were investigated in vivo. We found that flavopiridol and dinaciclib induced cytotoxicity by enhancing apoptosis in CDKN2A-defective SqCLC cells, and that epithelial to mesenchymal transition (EMT) decreased and autophagy increased during this process. In addition, we found that autophagy had a cytoprotective role. Our data suggest a potential role of CDK inhibitors in managing CDKN2A-defective SqCLC.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 5 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 5 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 2 40%
Unspecified 2 40%
Researcher 1 20%
Readers by discipline Count As %
Unspecified 2 40%
Agricultural and Biological Sciences 2 40%
Medicine and Dentistry 1 20%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 September 2018.
All research outputs
#10,074,479
of 12,593,681 outputs
Outputs from Cellular Oncology (2211-3428)
#70
of 156 outputs
Outputs of similar age
#201,401
of 268,954 outputs
Outputs of similar age from Cellular Oncology (2211-3428)
#4
of 11 outputs
Altmetric has tracked 12,593,681 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 156 research outputs from this source. They receive a mean Attention Score of 2.4. This one is in the 30th percentile – i.e., 30% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 268,954 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 14th percentile – i.e., 14% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 11 others from the same source and published within six weeks on either side of this one. This one is in the 27th percentile – i.e., 27% of its contemporaries scored the same or lower than it.