Evidence map›Paper›PMID 40499539›Full record

ArticleCell genomics2025

CXCR4-LASP1-G9a-SNAIL axis drives NEPC transdifferentiation via induction of EMT and downregulation of REST.

Liangliang Liu, Itzel Astiazarán Rascón, Dong Lin, Yuchao Ni, Xin Dong, Hui Xue, Yen-Yi Lin, Anne Haegert, Funda Sar, James W Peacock and 8 more

Abstract read
In one paragraph

Article in Cell genomics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. [A multi-level study of androgen deprivation therapy on the immune microenvironment in prostate cancer].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2026
    Article
  2. Review
  3. LASP1, a Novel Protein in Spermatozoa and Acrosome Reaction.Molecular reproduction and development · 2026
    Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Review
  9. 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

18 authors.

Liangliang LiuVancouver Prostate Centre, Vancouver, BC V6H 3Z6, Canada.
Itzel Astiazarán RascónBC Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada; Department of Radiology, University of British Columbia, Vancouver, BC V5Z 1M9, Canada.
Dong LinBC Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada.
Yuchao NiBC Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada.
Xin DongBC Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada.
Hui XueBC Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada.
Yen-Yi LinVancouver Prostate Centre, Vancouver, BC V6H 3Z6, Canada.
Anne HaegertVancouver Prostate Centre, Vancouver, BC V6H 3Z6, Canada.
Funda SarVancouver Prostate Centre, Vancouver, BC V6H 3Z6, Canada.
James W PeacockVancouver Prostate Centre, Vancouver, BC V6H 3Z6, Canada; Department of Urologic Sciences, University of British Columbia, Vancouver, BC V5Z 1M9, Canada.
Tabitha TombeVancouver Prostate Centre, Vancouver, BC V6H 3Z6, Canada.
Christopher DusekVancouver Prostate Centre, Vancouver, BC V6H 3Z6, Canada; Department of Urologic Sciences, University of British Columbia, Vancouver, BC V5Z 1M9, Canada.
Amina ZoubeidiVancouver Prostate Centre, Vancouver, BC V6H 3Z6, Canada; Department of Urologic Sciences, University of British Columbia, Vancouver, BC V5Z 1M9, Canada.
Martin E GleaveVancouver Prostate Centre, Vancouver, BC V6H 3Z6, Canada; Department of Urologic Sciences, University of British Columbia, Vancouver, BC V5Z 1M9, Canada.
Colin CollinsVancouver Prostate Centre, Vancouver, BC V6H 3Z6, Canada; Department of Urologic Sciences, University of British Columbia, Vancouver, BC V5Z 1M9, Canada.
Francois BénardBC Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada; Department of Radiology, University of British Columbia, Vancouver, BC V5Z 1M9, Canada. Electronic address: fbenard@bccrc.ca.
Yuzhuo WangVancouver Prostate Centre, Vancouver, BC V6H 3Z6, Canada; BC Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada; Department of Urologic Sciences, University of British Columbia, Vancouver, BC V5Z 1M9, Canada. Electronic address: ywang@bccrc.ca.
Christopher J OngVancouver Prostate Centre, Vancouver, BC V6H 3Z6, Canada; Department of Urologic Sciences, University of British Columbia, Vancouver, BC V5Z 1M9, Canada. Electronic address: chris.ong@ubc.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Phenotypic switching is an emerging driver of cancer treatment resistance, yet early signals regulating this process remain unclear. Here, using longitudinal single-cell RNA sequencing, we mapped differentiation trajectories in the LTL331 prostate adenocarcinoma patient-derived xenograft (PDX) model undergoing neuroendocrine prostate cancer (NEPC) transformation post castration. Our analyses identified a key differentiation node marked by epithelial-mesenchymal transition (EMT) and repressor element-1 silencing transcription factor (REST) downregulation driven by the CXCR4-LASP1-G9a-SNAIL axis. Mechanistically, CXCR4 activation promotes nuclear translocation of LASP1 that links G9a and SNAIL via SH3/proline-rich motif and LIM/SNAG domain interactions, enabling SNAIL-mediated REST repression via promoter E-box motifs. Inhibition of CXCR4 or G9a reversed LTL331R NEPC cells toward a luminal androgen receptor-active phenotype. CXCR4-targeted radioligands enabled both imaging and inhibition of NEPC tumors in vivo. These findings highlight the CXCR4-LASP1-G9a-SNAIL axis as a key regulator of epigenetic and transcriptional reprogramming in NEPC transdifferentiation and support its therapeutic targeting in aggressive NEPC.

Indexed as

Adaptor Proteins, Signal TransducingCell TransdifferentiationEpithelial-Mesenchymal TransitionLIM Domain ProteinsProstatic NeoplasmsReceptors, CXCR4Repressor ProteinsSnail Family Transcription FactorsAnimalsCell Line, TumorDown-RegulationGene Expression Regulation, NeoplasticHumansMaleMiceRE1-Silencing Transcription FactorAdaptor Proteins, Signal TransducingCXCR4 protein, humanLIM Domain ProteinsRE1-Silencing Transcription FactorReceptors, CXCR4Repressor ProteinsSNAI1 protein, humanSnail Family Transcription Factorscellular plasticityCXCR4epigenetic reprogrammingG9a histone methyl transferaseLASP1neuroendocrine prostate cancerpatient-derived xenograft modelsradiotherapySNAILtargeted therapeutictransdifferentiation

Identifiers

PMID40499539
PMCPMC12366657

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.