Evidence map›Paper›PMID 42415117›Full record

ArticleMolecular cancer2026

Targeting HASPIN-mediated H3T3 phosphorylation disrupts an epigenetic-kinesin axis to suppress colorectal cancer mitotic progression.

Tong Wu, Yaguang Zhang, Sicheng Liu, Chensong Zhang, Yang Zhang, Qiuye Luo, Dian Gao, Yang Meng, Yixin Jiang, Junhong Han

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cancer, 2026. 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
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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

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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

10 authors.

Tong Wu *Laboratory of Gastrointestinal Tumor Epigenetics and Genomics, State Key Laboratory of Biotherapy and Cancer Center, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, P.R. China.
Yaguang Zhang *Laboratory of Gastrointestinal Tumor Epigenetics and Genomics, State Key Laboratory of Biotherapy and Cancer Center, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, P.R. China.
Sicheng LiuLaboratory of Gastrointestinal Tumor Epigenetics and Genomics, State Key Laboratory of Biotherapy and Cancer Center, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, P.R. China.
Chensong ZhangLaboratory of Gastrointestinal Tumor Epigenetics and Genomics, State Key Laboratory of Biotherapy and Cancer Center, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, P.R. China.
Yang ZhangColorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, P.R. China.
Qiuye LuoLaboratory of Gastrointestinal Tumor Epigenetics and Genomics, State Key Laboratory of Biotherapy and Cancer Center, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, P.R. China.
Dian GaoLaboratory of Gastrointestinal Tumor Epigenetics and Genomics, State Key Laboratory of Biotherapy and Cancer Center, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, P.R. China.
Yang MengLaboratory of Gastrointestinal Tumor Epigenetics and Genomics, State Key Laboratory of Biotherapy and Cancer Center, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, P.R. China.
Yixin JiangLaboratory of Gastrointestinal Tumor Epigenetics and Genomics, State Key Laboratory of Biotherapy and Cancer Center, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, P.R. China.
Junhong HanLaboratory of Gastrointestinal Tumor Epigenetics and Genomics, State Key Laboratory of Biotherapy and Cancer Center, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, P.R. China. hjunhong@scu.edu.cn.

Funding

1·3·5 Project for Disciplines of Excellence, West China Hospital ZYGD23017National Key Research and Development Program of China 2022YFA1103702National Natural Science Foundation of China 82203447
6 · The paper itself

Abstract

Chemoresistance remains a major barrier in colorectal cancer (CRC) therapy. Through epigenetic compound screening in patient-derived organoids (PDOs), we identified CX6258.HCl as a potent growth inhibitor. Treatment with CX6258.HCl significantly inhibited cell mitosis and induced apoptosis in CRC cell lines. Mechanistically, CX6258.HCl binds the D687 residue within HASPIN's kinase domain, suppressing H3T3 phosphorylation (H3T3ph). This triggers an epigenetic cascade: loss of H3T3ph upregulates demethylase KDM5B pre-mRNA, depleting H3K4me3 at promoters of Kinesin family member (KIFC1/KIF10/KIF14). Consequently, microtubule dynamics are disrupted, leading to mitotic arrest. Target specificity was validated genetically via HASPIN-D687A mutation. In vivo, CX6258.HCl suppressed CRC xenograft growth and further enhanced 5-FU-mediated tumor suppression without obvious histological injury in major organs. Clinically, elevated H3T3ph levels in human CRC tissues were associated with Ki67-positive proliferative tumor regions, suggesting that H3T3ph may represent a proliferation-associated marker in CRC. Together, our findings identify the HASPIN/H3T3ph-KDM5B-H3K4me3-KIF axis as a targetable antimitotic pathway and support therapeutic inhibition of HASPIN/H3T3ph as a potential strategy for CRC.

Indexed as

Colorectal NeoplasmsEpigenesis, GeneticHistonesIntracellular Signaling Peptides and ProteinsKinesinsMitosisAnimalsApoptosisCell Line, TumorCell ProliferationGene Expression Regulation, NeoplasticHumansMicePhosphorylationProtein Serine-Threonine KinasesXenograft Model Antitumor AssaysHASPIN protein, humanHistonesIntracellular Signaling Peptides and ProteinsKinesinsProtein Serine-Threonine KinasesColorectal cancerCX6258.HClH3T3phKDM5BMitosisOrganoid

Identifiers

PMID42415117
PMCPMC13660172

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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.