Evidence map›Paper›PMID 42528528›Full record

ArticlebioRxiv : the preprint server for biology2026

A Stress-Adaptive Lipid Kinase Axis Defines Metabolic Vulnerabilities in Neuroendocrine Prostate Cancer.

Yang Zheng, Caleb Cheng, Yizhi Cao, Gabriel Cruz, Yuping Zhang, Radha Paturu, Somnath Mahapatra, Jing Hu, Rahul Mannan, Hüseyin Karabürk and 17 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 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

5 · Who and what money

Authors and funding

27 authors.

Yang ZhengMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Caleb ChengMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Yizhi CaoMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Gabriel CruzMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Yuping ZhangMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Radha PaturuMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Somnath MahapatraMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Jing HuMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Rahul MannanMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Hüseyin KarabürkDepartment of Cell & Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
Rupam BhattacharyyaMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Yitong YinMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Yi ZhaoMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Wenyan LiuMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Xuhong CaoMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Hui XueThe Vancouver Prostate Centre, Vancouver General Hospital and Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Chungen LiState Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, PRC.
Zhen WangState Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, PRC.
Stephanie J MinerMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Ulka VaishampayanDivision of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Vaibhav SahaiDivision of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Lois S WeismanDepartment of Cell & Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
Ke DingState Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, PRC.
Costas A LyssiotisRogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Yuzhuo WangThe Vancouver Prostate Centre, Vancouver General Hospital and Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Yuanyuan QiaoMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Arul M ChinnaiyanMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.

Funding

Tissue/InformaticsP50CA186786 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ARUL M CHINNAIYAN · 2014 to 2026
$27.6M
National Metabolomics Data Repository - nextgen Metabolomics WorkbenchU2CDK119886 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SUBRAMANIAM, SHANKAR · 2018 to 2021
$12.7M
Exploring Precision Oncology: From Gene Fusions to lncRNAsR35CA231996 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHINNAIYAN, ARUL M · 2018 to 2024
$6.4M
Michigan-VUMC Biomarker Characterization CenterU2CCA271854 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ARUL M CHINNAIYAN, Jeffrey John Tosoian · 2022 to 2026
$5.4M
Cellular and Molecular Biology at MichiganT32GM145470 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI John Chadwick Brenner · 2022 to 2026
$4.1M
Biomedical Data Commons Workbench (BDCW)OT2OD030544 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SUBRAMANIAM, SHANKAR · 2020 to 2024
$3.2M
Intratumoral Metabolic Crosstalk Promotes Therapeutic Resistance in Pancreatic CancerR37CA237421 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Costas Andreas Lyssiotis · 2020 to 2026
$2.6M
Regulation of parallel recycling pathways at synaptic sitesR01NS129198 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Michael Mark Alexander Sutton, Lois S Weisman · 2022 to 2026
$2.4M
Stromal metabolism promotes therapeutic resistance in pancreatic cancerR01CA248160 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LYSSIOTIS, COSTAS ANDREAS · 2020 to 2024
$2.0M
Targeting metabolic stress to induce pancreatic tumor cell deathR01CA244931 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LYSSIOTIS, COSTAS ANDREAS · 2020 to 2024
$1.9M
Targeting the lipid kinase PIKfyve in pancreatic ductal adenocarcinomaF30CA288093 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Caleb Cheng · 2025 to 2026
$87k
NCI NIH HHS F30 CA288093NCI NIH HHS P50 CA186786NCI NIH HHS R01 CA244931NCI NIH HHS R01 CA248160NCI NIH HHS R35 CA231996NCI NIH HHS R37 CA237421NCI NIH HHS U2C CA271854NIDDK NIH HHS U2C DK119886NIGMS NIH HHS T32 GM145470NIH HHS OT2 OD030544NINDS NIH HHS R01 NS129198
6 · The paper itself

Abstract

Neuroendocrine prostate cancer (NEPC) persists in a profoundly hypoxic microenvironment, yet the mechanisms enabling tumor adaptation to this metabolically challenging niche remain undefined. Here, we identify the lipid kinase PIKfyve as overexpressed in NEPC, functioning as a central node in a stress-lipid kinase axis that drives adaptation to persistent endoplasmic reticulum (ER) stress. Mechanistically, NEPC requires PIKfyve-mediated lysosomal degradation and lipid recycling to maintain metabolic homeostasis under hypoxia. PIKfyve inhibition disrupts lysosomal function, leading to ER stress accumulation and activation of a compensatory, sterol regulatory element-binding protein (SREBP)-dependent de novo lipogenesis program essential for NEPC survival. This stress-lipid axis creates a synthetic vulnerability between PIKfyve and fatty acid synthase (FASN), where dual inhibition synergistically amplifies ER stress, triggers the terminal unfolded protein response, and induces tumor cell death. These findings reveal a metabolic adaptation in NEPC and provide preclinical evidence that co-targeting PIKfyve and FASN can overcome hypoxia-associated stress adaptation.

Indexed as

ER stresslipid metabolismlysosomeneuroendocrine prostate cancerPIKfyve

Identifiers

PMID42528528
PMCPMC13411104

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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.