Evidence map›Paper›PMID 25675297›Full record

ArticleCell death & disease2015

p21-activated kinase 1 determines stem-like phenotype and sunitinib resistance via NF-κB/IL-6 activation in renal cell carcinoma.

Y Zhu, H Liu, L Xu, H An, W Liu, Y Liu, Z Lin, J Xu

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 14% 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

40 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.

  1. Pooled it
  2. Review
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  5. Article
  6. The Role of the p21-Activated Kinase Family in Tumor Immunity.International journal of molecular sciences · 2025
    Review
  7. Article
  8. Review
  9. Article
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  11. Review
  12. Review
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  15. Molecular mechanisms of resistance to tyrosine kinase inhibitor in clear cell renal cell carcinoma.International journal of urology : official journal of the Japanese Urological Association · 2022
    Review
  16. Review
  17. Article
  18. Article
  19. Article
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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

8 authors at 3 institutions in 1 country.

Y ZhuDepartment of Urology, Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, China.
H LiuKey Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Baskic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China.
L XuDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
H AnDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
W LiuKey Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Baskic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China.
Y LiuKey Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Baskic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China.
Z LinDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
J XuKey Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Baskic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai 200032, China.
Fudan University · CNShanghai Ninth People's Hospital · CNZhongshan Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The p21-activated kinase 1 (PAK1), a serine/threonine kinase that orchestrates cytoskeletal remodeling and cell motility, has been shown to function as downstream node for various oncogenic signaling pathways to promote cell proliferation, regulate apoptosis and accelerate mitotic abnormalities, resulting in tumor formation and invasiveness. Although alterations in PAK1 expression and activity have been detected in various human malignancies, its potential biological and clinical significance in renal cell carcinoma (RCC) remains obscure. In this study, we found increased PAK1 and phosphorylated PAK1 levels in tumor tissues according to TNM stage progression. Elevated phosphorylated PAK1 levels associated with progressive features and indicated unfavorable overall survival (OS) as an independent adverse prognosticator for patients with RCC. Moreover, PAK1 kinase activation with constitutive active PAK1 mutant T423E promoted growth, colony formation, migration, invasion and stem-like phenotype of RCC cells, and vice versa, in PAK1 inhibition by PAK1 kinase inactivation with specific PAK1 shRNA, dead kinase PAK1 mutant K299R or allosteric inhibitor IPA3. Stem-like phenotype due to sunitinib administration via increased PAK1 kinase activation could be ameliorated by PAK1 shRNA, PAK1 mutant K299R and IPA3. Furthermore, nuclear factor-κB (NF-κB)/interleukin-6 (IL-6) activation was found to be responsible for PAK1-mediated stem-like phenotype following sunitinib treatment. Both IL-6 neutralizing antibody and IPA3 administration enhanced tumor growth inhibition effect of sunitinib treatment on RCC cells in vitro and in vivo. Our results unraveled that oncogenic activation of PAK1 defines an important mechanism for maintaining stem-like phenotype and sunitinib resistance through NF-κB/IL-6 activation in RCC, lending PAK1-mediated NF-κB/IL-6 activation considerable appeal as novel pharmacological therapeutic targets against sunitinib resistance.

Indexed as

AnimalsAntineoplastic AgentsCarcinoma, Renal CellCell Line, TumorCell ProliferationCell SurvivalDrug Resistance, NeoplasmEnzyme-Linked Immunosorbent AssayHumansIndolesInterleukin-6MiceMice, NudeNF-kappa Bp21-Activated KinasesPhosphorylationAntineoplastic AgentsIL6 protein, humanIndolesInterleukin-6NF-kappa Bp21-Activated KinasesPAK1 protein, humanPyrrolesSunitinib

Identifiers

PMID25675297
PMCPMC4669810
OpenAlexW2026076390

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.