Evidence map›Paper›PMID 41559814›Full record

ArticleBreast cancer research : BCR2026

TRPS1 confers paclitaxel resistance in TNBC through dual activation of the PDE4D-cAMP-AKT pathway and microtubule destabilization.

Xin He, Wanting Tong, Xinyan Chen, Huifen Huang, Na Wei, Jiayue Ma, Yuqiong Liu, Yihui Ma, Shenglei Li, Wencai Li and 2 more

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Article in Breast cancer research : BCR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Xin HeDepartment of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Wanting TongDepartment of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Xinyan ChenUniversity of Pittsburgh, Pittsburgh, PA, USA.
Huifen HuangDepartment of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Na WeiDepartment of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Jiayue MaDepartment of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Yuqiong LiuDepartment of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Yihui MaDepartment of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Shenglei LiDepartment of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Wencai LiDepartment of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Huixiang LiDepartment of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Huayan RenDepartment of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. renhuayanhappy@163.com.

Funding

Key Research Project of Higher Education Institutions in Henan Province 24A310022National Natural Science Foundation of China 81803011
6 · The paper itself

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype that lacks effective targeted therapies and frequently develops resistance to paclitaxel, with the underlying mechanisms remaining incompletely understood. Clinically, elevated TRPS1 expression was significantly associated with poor pathological response to neoadjuvant chemotherapy and reduced overall survival in TNBC patients. Mechanistically, we identified phosphodiesterase 4D (PDE4D) as a direct transcriptional target of TRPS1 and showed that TRPS1-driven PDE4D upregulation promotes paclitaxel resistance by activating cAMP–PI3K–AKT survival signaling and destabilizing microtubules. Importantly, pharmacological inhibition of PDE4D with roflumilast, an FDA-approved PDE4 inhibitor, restored cAMP signaling, suppressed AKT activation, improved microtubule stability, and resensitized TRPS1-high TNBC models to paclitaxel in vitro and in vivo. Together, these findings define the TRPS1–PDE4D axis as a previously unrecognized driver of paclitaxel resistance in TNBC, support TRPS1 as a potential predictive biomarker of treatment response, and suggest that repurposing roflumilast may represent a promising therapeutic strategy to overcome paclitaxel resistance in TRPS1-overexpressing TNBC.

Indexed as

Cyclic Nucleotide Phosphodiesterases, Type 4DNA-Binding ProteinsDrug Resistance, NeoplasmMicrotubulesPaclitaxelProto-Oncogene Proteins c-aktTranscription FactorsTriple Negative Breast NeoplasmsAminopyridinesAnimalsBenzamidesCell Line, TumorCyclic AMPCyclopropanesFemaleGene Expression Regulation, NeoplasticAminopyridinesBenzamidesCyclic AMPCyclic Nucleotide Phosphodiesterases, Type 4CyclopropanesDNA-Binding ProteinsPaclitaxelPDE4D protein, humanProto-Oncogene Proteins c-aktRoflumilastTranscription FactorsChemoresistanceMicrotubule dynamicsPDE4DRoflumilastTriple-negative breast cancerTRPS1

Identifiers

PMID41559814
PMCPMC12903692

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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.