Evidence map›Paper›PMID 40590665›Full record

ArticleCancer science2025

KLHL5 Contributes to Colorectal Cancer Cell Survival by Promoting Cell Cycle Progression and Suppressing Apoptotic Cell Death.

Kyosuke Habu, Yosuke Matsuoka, Hiromi Hiyoshi, Jun Nakayama, Katsuya Watanabe, Sota Tate, Tomohisa Sakaue, Junko Murai, Konomu Uno, Hirotada Nishie and 6 more

Abstract read
In one paragraph

Article in Cancer science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

16 authors.

Kyosuke HabuDepartment of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Toon, Japan.
Yosuke MatsuokaDepartment of Oncogenesis and Growth Regulation, Osaka International Cancer Institute, Osaka, Japan.
Hiromi HiyoshiDepartment of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Jun NakayamaDepartment of Oncogenesis and Growth Regulation, Osaka International Cancer Institute, Osaka, Japan.ORCID https://orcid.org/0000-0001-8844-4295
Katsuya WatanabeDepartment of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Toon, Japan.
Sota TateDepartment of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Toon, Japan.
Tomohisa SakaueDepartment of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Toon, Japan.
Junko MuraiDepartment of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Toon, Japan.
Konomu UnoDepartment of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Hirotada NishieDepartment of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Eiji KubotaDepartment of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Hiromi KataokaDepartment of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.ORCID https://orcid.org/0000-0001-9491-0723
Takashi JohDepartment of Gastroenterology, Gamagori Municipal Hospital, Gamagori, Japan.
Yuji WatanabeDepartment of Gastrointestinal Surgery and Surgical Oncology, Ehime University Graduate School of Medicine, Toon, Japan.
Taro OshikiriDepartment of Gastrointestinal Surgery and Surgical Oncology, Ehime University Graduate School of Medicine, Toon, Japan.
Shigeki HigashiyamaDepartment of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Toon, Japan.ORCID https://orcid.org/0000-0002-2417-3921

Funding

Japan Society for the Promotion of Science KAKENHI Number 19K09123
6 · The paper itself

Abstract

Kelch-like protein 5 (KLHL5) is highly expressed in colorectal cancer (CRC) compared to that in adjacent normal mucosa, and its expression level increases with CRC stage, showing a correlation with poor prognostic factors. However, its functional role in the malignant progression still remains unknown. To elucidate the role of KLHL5 in CRC, we characterized human CRC cell lines, including HCT116 and SW480, under KLHL5-depleted conditions. KLHL5-depleted HCT116 and SW480 cells suppressed their growth and migration in culture. Further duration induced cell death characterized by apoptotic cell death with down-regulation of antiapoptotic factor Bcl-2 and up-regulation of proapoptotic factors Bac, Boc, Puma, Bid, Noxa, and Bik. Proteomic analyses indicated KLHL5 depletion suppressed cell cycle progression by affecting multiple pathways, including the activation of the G2/M DNA damage pathway and inhibition of the G1/S transition. Further biochemical and cell biological analyses revealed the downregulation of CDT1 and CDC6 proteins, which are essential factors for the initiation of DNA replication, and the downregulation of cyclins A and B, which are essential factors for the progression of S and G2/M phases. Arrested cells undergo apoptotic cell death. Taken together, these data strongly indicate that KLHL5 expression in CRC serves as a survival factor to strengthen the cell cycle and protect against apoptotic cell death under harsh tumor microenvironments.

Indexed as

ApoptosisCell CycleColorectal NeoplasmsApoptosis Regulatory ProteinsCell Cycle ProteinsCell Line, TumorCell MovementCell ProliferationCell SurvivalGene Expression Regulation, NeoplasticHCT116 CellsHumansProteomicsApoptosis Regulatory ProteinsCell Cycle Proteinsanti‐cell deathbiomarkercell cyclecolorectal cancerKLHL5

Identifiers

PMID40590665
PMCPMC12400063

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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.