Evidence map›Paper›PMID 41933135›Full record

ArticleOncogene2026

TWIST1 mediated transcriptional activation of SPON2 drives colorectal cancer peritoneal metastasis through stromal cell signaling network.

Zhuan Zhou, Alessandro La Ferlita, Manoj H Palavalli, Xiongfeng Chen, Lauren Tyler, Aslam Ejaz, Joal Beane, Patricio M Polanco, Huocong Huang, Alex C Kim

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 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
–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

10 authors.

Zhuan ZhouDivision of Surgical Oncology, Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA.
Alessandro La FerlitaDivision of Medical Oncology, Department of Medicine, The Ohio State University Wexner Medical Center, the James Comprehensive Cancer Center and Solove Research Institute, Ohio State University, Columbus, OH, USA.
Manoj H PalavalliDivision of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, the James Comprehensive Cancer Center and Solove Research Institute, Ohio State University, Columbus, OH, USA.
Xiongfeng ChenDivision of Surgical Oncology, Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA.
Lauren TylerDivision of Surgical Oncology, Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA.
Aslam EjazDepartment of Surgery, Section of General Surgery and Surgical Oncology, University of Illinois-Chicago, Chicago, IL, USA.
Joal BeaneDivision of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, the James Comprehensive Cancer Center and Solove Research Institute, Ohio State University, Columbus, OH, USA.
Patricio M PolancoDivision of Surgical Oncology, Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA.
Huocong HuangDivision of Surgical Oncology, Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA. huocong.huang@utsouthwestern.edu.ORCID http://orcid.org/0000-0002-6345-4566
Alex C KimDivision of Surgical Oncology, Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA. alex.kim@utsouthwestern.edu.ORCID http://orcid.org/0000-0003-3113-6560

Funding

Function of mesothelial cells in the tumor microenvironment of pancreatic ductal adenocarcinomaR00CA252009 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI HUANG, HUOCONG · 2023 to 2025
$747k
A phase-1 trial of intraperitoneal 5-fluorouracil and oxaliplatin in patients with colorectal cancer and unresectable peritoneal metastasis.R21CA282536 · NCI · OHIO STATE UNIVERSITY · PI KIM, ALEX C., MITTRA, ARJUN · 2023 to 2023
$336k
NCI NIH HHS R00 CA252009NCI NIH HHS R21 CA282536
6 · The paper itself

Abstract

Colorectal cancer (CRC) peritoneal metastasis (PM) accounts for 25-35% of stage IV cases. CRC PM carries a median overall survival of 16 months with systemic chemotherapy and an almost 0% 5-year survival rate. The molecular mechanisms driving CRC PM remain poorly defined. CRC heterogeneity is classified into four Consensus Molecular Subtypes (CMS1-4), with CRC PM predominantly exhibiting the CMS4 signature-characterized by increased stromal/mesenchymal enrichment and cellular plasticity-features linked to frequent disease progression and therapeutic resistance. Here, we investigated the molecular mechanisms driving CRC PM and CMS4 signature. TWIST1 was identified to be significantly upregulated in CRC PM. We established TWIST1-SPON2 as a novel transcriptional axis contributing to CRC PM tumorigenesis, through mediating tumor-stroma interactions. We identified SPP1, secreted by the tumor stroma, as an upstream regulator of the TWIST1-SPON2 cascade via AKT activation in tumor cells in vitro and in vivo. This defined SPP1-TWIST1-SPON2 signaling circuit is pivotal in shaping the tumor microenvironment and promoting CRC PM progression. The findings establish the SPP1-TWIST1-SPON2 axis as potential biomarkers and therapeutic targets in CRC PM.

Indexed as

Colorectal NeoplasmsNuclear ProteinsPeritoneal NeoplasmsStromal CellsTwist-Related Protein 1AnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansMiceOsteopontinSignal TransductionTranscriptional ActivationTumor MicroenvironmentNuclear ProteinsOsteopontinTWIST1 protein, humanTwist-Related Protein 1

Identifiers

PMID41933135
PMCPMC13099403

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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.