Evidence map›Paper›PMID 31807020›Full record

ArticleOncoTargets and therapy2019

DNA-PKcs Mediates An Epithelial-Mesenchymal Transition Process Promoting Cutaneous Squamous Cell Carcinoma Invasion And Metastasis By Targeting The TGF-β1/Smad Signaling Pathway.

Juan Zhang, Hui Jiang, Dan Xu, Wen-Juan Wu, Hong-Duo Chen, Li He

Open access · goldAbstract read
In one paragraph

Article in OncoTargets and therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.9field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 14 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Juan Zhang *Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Institute of Dermatology & Venereology of Yunnan Province, Kunming, People's Republic of China.
Hui Jiang *Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Institute of Dermatology & Venereology of Yunnan Province, Kunming, People's Republic of China.
Dan Xu *Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Institute of Dermatology & Venereology of Yunnan Province, Kunming, People's Republic of China.
Wen-Juan WuDepartment of Dermatology, First Affiliated Hospital of Kunming Medical University, Institute of Dermatology & Venereology of Yunnan Province, Kunming, People's Republic of China.ORCID 0000-0002-1138-9096
Hong-Duo ChenDepartment of Dermatology, The First Hospital of China Medical University, Shenyang, People's Republic of China.
Li HeDepartment of Dermatology, First Affiliated Hospital of Kunming Medical University, Institute of Dermatology & Venereology of Yunnan Province, Kunming, People's Republic of China.
Kunming Medical University · CNFirst Hospital of China Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeDNA-dependent protein kinase catalytic subunit (DNA-PKcs) has attracted extensive attention in various types of malignant tumors. However, the role of DNA-PKcs in cutaneous squamous cell carcinoma (cSCC) development has not been elucidated. In this study, we investigated the role of DNA-PKcs in cSCC and the molecular mechanisms of TGF-β1-induced cSCC progression mediated by DNA-PKcs.

methodsWe performed bioinformatic analysis and RT-PCR to examine the DNA-PKcs expression level in cSCC. Then, we downregulated DNA-PKcs using a DNA-PK-specific inhibitor or small interfering RNA (siRNA) to explore the effects of DNA-PKcs on SCL-1 cell migration and invasion. To further investigate the mechanism by which DNA-PKcs promotes cSCC progression, TGF-β1 and the TGF-β receptor (TGF-βR) I/II dual inhibitor LY2109761 were used to examine whether DNA-PKcs participates in TGF-β1/Smad signaling.

resultsDNA-PKcs expression was upregulated in cSCC. DNA-PK inhibition or expression knockdown resulted in inhibited migration and invasion and altered epithelial-mesenchymal transition (EMT) marker expression patterns in SCL-1 cells. Importantly, TGF-β1 mediated EMT induction in cSCC cells, and DNA-PKcs was identified as a TGF-β1-responsive gene. TGF-β1 promoted DNA-PKcs transcription, and DNA-PKcs enhanced the TGF-β1-induced EMT program involved in cSCC invasion and metastasis by phosphorylating Smad3.

conclusionThis study is the first to show that DNA-PKcs mediates EMT to promote cSCC aggressiveness by targeting the TGF-β1/Smad signaling pathway, which provides insight into how DNA-PKcs impacts cSCC progression and identifies a new therapeutic target.

Indexed as

cutaneous squamous cell carcinomaDNA-dependent protein kinase catalytic subunitE-cadherinepithelial-mesenchymal transitiontransforming growth factor-β1

Identifiers

PMID31807020
PMCPMC6844265
OpenAlexW2988503068

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.