Evidence map›Paper›PMID 40228761›Full record

ArticlePharmacological research2025

Sex-specific effects of exogenous asparagine on colorectal tumor growth, 17β-estradiol levels, and aromatase.

Oladimeji Aladelokun, Katherine Benitez, Yuying Wang, Abhishek Jain, Domenica Berardi, Georgio Maroun, Xinyi Shen, Jatin Roper, Joanna Gibson, Kaelyn Sumigray and 2 more

Abstract read
In one paragraph

Article in Pharmacological research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

12 authors.

Oladimeji AladelokunDepartment of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA.
Katherine BenitezDepartment of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA; Program in Translational Biomedicine, Yale University School of Medicine, New Haven, CT, USA.
Yuying WangDepartment of Genetics, Yale School of Medicine, New Haven, CT, USA.
Abhishek JainDepartment of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA.
Domenica BerardiDepartment of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA.
Georgio MarounDepartment of Molecular Biochemistry and Biophysics, Yale University, New Haven, CT, USA.
Xinyi ShenDepartment of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA.
Jatin RoperDivision of Gastroenterology, Department of Medicine, Duke University School of Medicine, NC, USA.
Joanna GibsonDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.
Kaelyn SumigrayDepartment of Genetics, Yale School of Medicine, New Haven, CT, USA.
Sajid A KhanDivision of Surgical Oncology, Department of Surgery, Yale School of Medicine, New Haven, CT, USA. Electronic address: sajid.khan@yale.edu.
Caroline H JohnsonDepartment of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, USA. Electronic address: caroline.johnson@yale.edu.

Funding

The Yale Cancer Prevention and Control Training ProgramT32CA250803 · NCI · YALE UNIVERSITY · PI Melinda L Irwin, Xiaomei Ma · 2020 to 2026
$2.3M
Wnt signaling in obesity-associated colorectal cancerR37CA259363 · NCI · DUKE UNIVERSITY · PI Jatin Roper · 2022 to 2026
$1.8M
Role and Regulation of Asparagine in Colorectal CancerR01CA289440 · NCI · YALE UNIVERSITY · PI Caroline Helen Johnson, Sajid A Khan · 2025 to 2026
$1.4M
NCI NIH HHS R01 CA289440NCI NIH HHS R37 CA259363NCI NIH HHS T32 CA250803
6 · The paper itself

Abstract

Sex-related differences in asparagine metabolism are associated with cancer prognosis. However, the effect of exogenous asparagine on colorectal cancer (CRC) growth in men and women remains unclear. This study aims to understand the relationship between exogenous asparagine supplementation and 17β-estradiol levels and to elucidate mechanisms underlying sex-dependent signaling during CRC development. We administered asparagine intraperitoneally to tumor-bearing male and female immunodeficient Rag2/Il2RG (R2G2) mice. Asparagine supplementation caused a significant increase in tumor asparagine levels in both the tumor-bearing male and female R2G2 mice but increased serum estradiol levels and suppressed tumor growth in female R2G2 mice only. Additionally, we combined transcriptome, metabolome, and immunochemical analyses, and found that intraperitoneal asparagine treatment induced sex-dependent intra-tumoral metabolic changes to asparagine, aspartate, glutamine and glutamate levels. We observed that in females, exogenous asparagine exerts a negative feed-back effect on de novo asparagine synthesis and is associated with the activation of a sub-population of macrophages that may secrete 17β-estradiol via an aromatase or cytochrome P450 family 19 (CYP19)-dependent mechanism. Conversely, in male mice, asparagine treatment augments tumor growth, and is related to decreased numbers of macrophages, and a reduction in CYP19-mediated 17β-estradiol secretion . Overall, our results reveal a novel and sex-specific role for exogenous asparagine during cancer progression and underscores the importance of understanding mechanisms that control asparagine biosynthesis.

Indexed as

AromataseAsparagineColorectal NeoplasmsEstradiolAnimalsCell Line, TumorFemaleMacrophagesMaleMiceSex CharacteristicsSex FactorsAromataseAsparagineEstradiolAromataseAsparagineEstrogen signalingGastrointestinal cancer- colorectalPre-clinical modelsSex differences

Identifiers

PMID40228761
PMCPMC12100670

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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.