Evidence map›Paper›PMID 38926346›Full record

ArticleCell death & disease2024

ASAH1 facilitates TNBC by DUSP5 suppression-driven activation of MAP kinase pathway and represents a therapeutic vulnerability.

Kiran Kumar Reddi, Suresh Chava, Siva Chander Chabattula, Yvonne J K Edwards, Kamaljeet Singh, Romi Gupta

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Review
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  5. 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

6 authors.

Kiran Kumar ReddiDepartment of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL, USA.
Suresh ChavaDepartment of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL, USA.ORCID 0000-0002-9360-5249
Siva Chander ChabattulaDepartment of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL, USA.
Yvonne J K EdwardsDepartment of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL, USA.
Kamaljeet SinghDepartment of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA.
Romi GuptaDepartment of Biochemistry and Molecular Genetics, The University of Alabama at Birmingham, Birmingham, AL, USA. romigup@uab.edu.ORCID 0000-0001-5108-5962

Funding

XRAY CRYSTALLOGRAPHYP30CA013148 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Omer Jamy · 1985 to 2026
$165.9M
PRECISION METABOLIC THERAPY OF p53 MUTANT TRIPLE NEGATIVE BREAST CANCERSR01CA233481 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI GUPTA, ROMI · 2021 to 2025
$1.6M
A NOVEL EPIGENETIC IMMUNOTHERAPY FOR OVARIAN CANCER TREATMENTR03CA230815 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI GUPTA, ROMI · 2019 to 2020
$149k
A Novel Anoikis Effector that Drives Ovarian Cancer MetastasisR03CA248913 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI GUPTA, ROMI · 2020 to 2021
$149k
NCI NIH HHS P30 CA013148NCI NIH HHS R01 CA233481NCI NIH HHS R03 CA230815NCI NIH HHS R03 CA248913U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA233481U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R03CA230815U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R03CA248913
6 · The paper itself

Abstract

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is prone to metastasis and therapy resistance. Owing to its aggressive nature and limited availability of targeted therapies, TNBC is associated with higher mortality as compared to other forms of breast cancer. In order to develop new therapeutic options for TNBC, we characterized the factors involved in TNBC growth and progression. Here, we demonstrate that N-acylsphingosine amidohydrolase 1 (ASAH1) is overexpressed in TNBC cells and is regulated via p53 and PI3K-AKT signaling pathways. Genetic knockdown or pharmacological inhibition of ASAH1 suppresses TNBC growth and progression. Mechanistically, ASAH1 inhibition stimulates dual-specificity phosphatase 5 (DUSP5) expression, suppressing the mitogen-activated protein kinase (MAPK) pathway. Furthermore, pharmacological cotargeting of the ASAH1 and MAPK pathways inhibits TNBC growth. Collectively, we unmasked a novel role of ASAH1 in driving TNBC and identified dual targeting of the ASAH1 and MAPK pathways as a potential new therapeutic approach for TNBC treatment.

Indexed as

Acid CeramidaseDual-Specificity PhosphatasesMAP Kinase Signaling SystemTriple Negative Breast NeoplasmsAnimalsCell Line, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansMiceMice, NudePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSignal TransductionTumor Suppressor Protein p53Acid CeramidaseASAH1 protein, humanDual-Specificity PhosphatasesDUSP5 protein, humanPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktTumor Suppressor Protein p53

Identifiers

PMID38926346
PMCPMC11208621

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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.