Evidence map›Paper›PMID 39821099›Full record

ArticleOncogene2025

Oncogenic potential of truncated-Gli3 via the Gsk3β/Gli3/AR-V7 axis in castration-resistant prostate cancer.

Jyoti B Kaushal, Pratima Raut, Sushanta Halder, Zahraa W Alsafwani, Seema Parte, Gunjan Sharma, K M Abdullah, Parthasarathy Seshacharyulu, Subodh M Lele, Surinder K Batra and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. 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

11 authors.

Jyoti B KaushalDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA. jyoti.kaushal@unmc.edu.
Pratima RautDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Sushanta HalderDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Zahraa W AlsafwaniDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Seema ParteDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Gunjan SharmaDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
K M AbdullahDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Parthasarathy SeshacharyuluDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.ORCID http://orcid.org/0000-0002-2348-3901
Subodh M LeleDepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
Surinder K BatraDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA. sbatra@unmc.edu.ORCID http://orcid.org/0000-0001-9470-9317
Jawed A SiddiquiDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA. jsiddiqui@umc.edu.ORCID http://orcid.org/0000-0003-1287-3004

Funding

United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP) DOD W81XWH-18-1-0308United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP) DOD W81XWH-21-1-0340United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs (CDMRP) W81XWH-21-1-0640
6 · The paper itself

Abstract

The functional activation of the androgen receptor (AR) and its interplay with the aberrant Hh/Gli cascade are pivotal in the progression of castration-resistant prostate cancer (CRPC) and resistance to AR-targeted therapies. Our study unveiled a novel role of the truncated form of Gli (t-Gli3) in advancing CRPC. Investigation into Gli3 regulation revealed a Smo-independent mechanism for its activation. Despite lacking a transactivation domain, t-Gli3 relies on androgen receptor variant 7 (AR-V7) for its action. Mechanistically, Gsk3β activation led to the t-Gli3 generation, and inhibition of Gsk3β supported the accumulation of full-length Gli3 expression through a non-canonical mechanism. Knockdown of Gsk3β (Gsk3β KD) reduces CRPC cell proliferation, induces apoptosis via mitochondrial fragmentation, and triggers metabolomic reprogramming. The in vivo studies with Gsk3β KD cells in the mouse prostate resulted in tumor growth retardation compared to scramble cells. RNA-seq HALLMARK Gene Set Enrichment Analysis (GSEA) analysis of Gsk3β KD revealed a positive enrichment of apoptosis, tumor suppressor gene, and negative enrichment of oncogenic pathway. Furthermore, combinational use of a Gsk3β inhibitor with anti-Smo or Gli1 significantly inhibited the CRPC cell growth, which is resistant to individual Smo or Gli1 inhibitor targeting. Intriguingly, solely targeting Gli3 showed effectiveness in inhibiting CRPC cell growth. Overall, our study underscores the clinical significance of Gli3, emphasizing t-Gli3, and provides novel insights into the interplay of the Gsk3β/t-Gli3/AR-V7 axis in CRPC.

Indexed as

Glycogen Synthase Kinase 3 betaNerve Tissue ProteinsProstatic Neoplasms, Castration-ResistantReceptors, AndrogenZinc Finger Protein Gli3AnimalsApoptosisCell Line, TumorCell ProliferationGene Expression Regulation, NeoplasticHumansMaleMiceSignal TransductionAR protein, humanGLI3 protein, humanGlycogen Synthase Kinase 3 betaGSK3B protein, humanNerve Tissue ProteinsReceptors, AndrogenZinc Finger Protein Gli3

Identifiers

PMID39821099
PMCPMC11976299

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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.