Evidence map›Paper›PMID 36851883›Full record

ArticleCancer science2023

Inhibition of protein kinase C delta leads to cellular senescence to induce anti-tumor effects in colorectal cancer.

Yuya Shimoyama, Kohji Yamada, Saishu Yoshida, Akira Kawamura, Yoshito Hannya, Yuta Imaizumi, Tomotaka Kumamoto, Yasuhiro Takeda, Masayuki Shimoda, Ken Eto and 1 more

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

Article in Cancer science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.7field-weighted citation impact, top 24% 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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Article
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

11 authors at 1 institution in 1 country.

Yuya ShimoyamaDepartment of Biochemistry, The Jikei University School of Medicine, Tokyo, Japan.
Kohji YamadaDepartment of Biochemistry, The Jikei University School of Medicine, Tokyo, Japan.ORCID https://orcid.org/0000-0001-9493-5269
Saishu YoshidaDepartment of Biochemistry, The Jikei University School of Medicine, Tokyo, Japan.
Akira KawamuraDepartment of Biochemistry, The Jikei University School of Medicine, Tokyo, Japan.
Yoshito HannyaDepartment of Biochemistry, The Jikei University School of Medicine, Tokyo, Japan.
Yuta ImaizumiDepartment of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
Tomotaka KumamotoDepartment of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
Yasuhiro TakedaDepartment of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
Masayuki ShimodaDepartment of Pathology, The Jikei University School of Medicine, Tokyo, Japan.
Ken EtoDepartment of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
Kiyotsugu YoshidaDepartment of Biochemistry, The Jikei University School of Medicine, Tokyo, Japan.ORCID https://orcid.org/0000-0003-3108-7383
Jikei University School of Medicine · JP

Funding

Japan Society for the Promotion of Science JP16K18434Japan Society for the Promotion of Science JP17H03584Japan Society for the Promotion of Science JP18K15253Japan Society for the Promotion of Science JP18K19484Japan Society for the Promotion of Science JP20H03519Japan Society for the Promotion of Science JP20K07621
6 · The paper itself

Abstract

Protein kinase C delta (PKCδ) is a multifunctional serine-threonine kinase implicated in cell proliferation, differentiation, tumorigenesis, and therapeutic resistance. However, the molecular mechanism of PKCδ in colorectal cancer (CRC) remains unclear. In this study, we showed that PKCδ acts as a negative regulator of cellular senescence in p53 wild-type (wt-p53) CRC. Immunohistochemical analysis revealed that PKCδ levels in human CRC tissues were higher than those in the surrounding normal tissues. Deletion studies have shown that cell proliferation and tumorigenesis in wt-p53 CRC is sensitive to PKCδ expression. We found that PKCδ activates p21 via a p53-independent pathway and that PKCδ-kinase activity is essential for p21 activity. In addition, both repression of PKCδ expression and inhibition of PKCδ activity induced cellular senescence-like phenotypes, including increased senescence-associated β-galactosidase (SA-β-gal) staining, low LaminB1 expression, large nucleus size, and senescence-associated secretory phenotype (SASP) detection. Finally, a kinase inhibitor of PKCδ suppressed senescence-dependent tumorigenicity in a dose-dependent manner. These results offer a mechanistic insight into CRC survival and tumorigenesis. In addition, a novel therapeutic strategy for wt-p53 CRC is proposed.

Indexed as

Colorectal NeoplasmsProtein Kinase C-deltaCarcinogenesisCellular SenescenceCyclin-Dependent Kinase Inhibitor p21HumansTumor Suppressor Protein p53Cyclin-Dependent Kinase Inhibitor p21Protein Kinase C-deltaTumor Suppressor Protein p53cellular senescencecolorectal cancerkinase inhibitorprotein kinase C deltatumorigenesis

Identifiers

PMID36851883
PMCPMC10236638
OpenAlexW4322617138

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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 Socratic graph.