Evidence map›Paper›PMID 40483692›Full record

ArticleCell reports2025

Cholesterol metabolism regulated by CAMKK2-CREB signaling promotes castration-resistant prostate cancer.

Chenchu Lin, Thomas L Pulliam, Jenny J Han, Jiaqian Xu, Carlos Vera Recio, Sandi R Wilkenfeld, Yan Shi, Manoj Kushwaha, Sarah Bench, Eduardo Ruiz and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. 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. Article
  3. Article
  4. Review
  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

20 authors.

Chenchu LinDepartment of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; UTHealth Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center Houston, TX 77030, USA; Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Thomas L PulliamDepartment of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Jenny J HanDepartment of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Jiaqian XuDepartment of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Carlos Vera RecioDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Sandi R WilkenfeldDepartment of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; UTHealth Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center Houston, TX 77030, USA.
Yan ShiDepartment of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Manoj KushwahaDepartment of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
Sarah BenchDepartment of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
Eduardo RuizDepartment of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Sanjanaa SenthilkumarDepartment of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Mayo Clinic Alix School of Medicine, Phoenix, AZ 85054, USA.
Jayasurya DileepDepartment of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; McKetta Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78712, USA.
Peter D A ShepherdDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Nora M NavoneDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Albert R KlekersDepartment of Abdominal Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Elizabeth M WhitleyDepartment of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Michael M IttmannDepartments of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Houston, TX 77030, USA; Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX 77030, USA.
Livia S EberlinDepartment of Surgery, Baylor College of Medicine, Houston, TX 77030, USA; Department of Chemistry, The University of Texas at Austin, Austin, TX 78712, USA.
Wenyi WangDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Daniel E FrigoDepartment of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, TX 77204, USA; Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, USA. Electronic address: frigo@mdanderson.org.

Funding

TRAINING PROGRAM IN COMPUTATIONAL BIOLOGY AND MEDICINET15LM007093 · NLM · RICE UNIVERSITY · PI Lydia E. Kavraki · 1992 to 2026
$20.8M
Genetic & Metabolic Dissection of the CaMKKbeta Signaling Axis in Prostate CancerR01CA184208 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI FRIGO, DANIEL EDWARD · 2015 to 2019
$1.9M
NCI NIH HHS R01 CA184208NLM NIH HHS T15 LM007093
6 · The paper itself

Abstract

Castration-resistant prostate cancer (CRPC) remains an incurable disease in need of improved treatments. CAMKK2 is an emerging therapeutic target whose oncogenic effects in prostate cancer have, to date, been largely attributed to its activation of AMP-activated protein kinase (AMPK). Here, we demonstrate that CAMKK2 promotes prostate cancer growth through an alternative downstream pathway involving CAMKI and CREB. Unbiased transcriptomics identify CREB-mediated transcription as a CAMKK2-regulated process, findings that we validate using diverse molecular, genetic, and pharmacological approaches in vitro and in vivo. CAMKK2 promotes CREB phosphorylation/activation through CAMKIα independently of AMPK, CAMKIV, or other CAMKI isoforms. Functionally, the CREB family members CREB1 and ATF1 exhibit close redundancy, necessitating co-targeting for optimal anti-tumor efficacy. An inhibitor of CREB1/ATF1 blocks CRPC with minimal side effects. Mechanistically, CAMKK2 and CREB increase CRPC growth through augmenting cholesterol metabolism. Together, these findings identify an oncogenic pathway that could be exploited for the treatment of CRPC.

Indexed as

Calcium-Calmodulin-Dependent Protein Kinase KinaseCholesterolCyclic AMP Response Element-Binding ProteinProstatic Neoplasms, Castration-ResistantSignal TransductionAMP-Activated Protein KinasesAnimalsCell Line, TumorCell ProliferationHumansMaleMicePhosphorylationAMP-Activated Protein KinasesCalcium-Calmodulin-Dependent Protein Kinase KinaseCAMKK2 protein, humanCholesterolCREB1 protein, humanCyclic AMP Response Element-Binding ProteinAMPKandrogen receptorCAMKICAMKK2cholesterolCP: CancerCP: MetabolismCREBmetabolismprostate cancer

Identifiers

PMID40483692
PMCPMC12289408

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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 Socratic graph.