Evidence map›Paper›PMID 41896862›Full record

ArticleCell communication and signaling : CCS2026

The hexosamine biosynthetic pathway alters the cytoskeleton to modulate cell proliferation and migration in aggressive prostate cancer.

Rajina Shakya, Praveen Suraneni, Amit Rahi, Michael Y Young, Emily Cousino, Christine B Magdongon, Raju Gajjela, Basil B Mattamana, Alexander Zaslavsky, Ganesh S Palapattu and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell communication and signaling : CCS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Rajina Shakya *Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
Praveen Suraneni *Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
Amit RahiDepartment of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
Michael Y YoungDepartment of Urology, University of Michigan Medical School, Ann Harbor, MI, 48108, USA.ORCID http://orcid.org/0009-0009-3990-5724
Emily CousinoDepartment of Urology, University of Michigan Medical School, Ann Harbor, MI, 48108, USA.
Christine B MagdongonDepartment of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
Raju GajjelaProteomics Core, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
Basil B MattamanaProteomics Core, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
Alexander ZaslavskyDepartment of Urology, University of Michigan Medical School, Ann Harbor, MI, 48108, USA.
Ganesh S PalapattuDepartment of Urology, University of Michigan Medical School, Ann Harbor, MI, 48108, USA.
Arun SreekumarDepartment of Molecular and Cellular Biology and Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, TX, 77030, USA.
Dileep VarmaDepartment of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA. dvarma14@yahoo.com.

Funding

Targeting FOXA1-downstream pathways: a novel therapeutic strategy for castration-resistant prostate cancerP50CA180995 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ABDULKADIR, SARKI A., HUSSAIN, MAHA H · 2015 to 2025
$19.9M
NCI NIH HHS P50 CA180995NIGMS NIH HHS GM135391
6 · The paper itself

Abstract

Castration-resistant prostate cancer (CRPC) progresses despite androgen deprivation therapy, as cancer cells adapt to grow without testosterone, becoming more aggressive and prone to metastasis. CRPC biology complicates the development of effective therapies, posing challenges for patient care. Recent gene-expression and metabolomics studies highlight the Hexosamine Biosynthetic Pathway (HBP) as a critical player, with key components like GNPNAT1 (Glucosamine-phosphate N-acetyltransferase 1) being downregulated in CRPC. GNPNAT1 knockdown in pre-clinical models has been shown to increase growth and metastasis in CRPC tumors, though the mechanisms remain unclear.To investigate the cellular basis of these CRPC phenotypes, we generated a CRISPR-Cas9 knockout model of GNPNAT1 in 22Rv1 CRPC cells, analyzing its impact on transcriptomic and glycoproteomic profiles of cells. We find that HBP inhibition disrupts the cytoskeleton, altering mitotic progression and promoting uncontrolled growth. GNPNAT1 KO cells showed reduced levels of cytoskeletal filaments, such as actin and microtubules, leading to cell structure disorganization and chromosomal mis-segregation. GNPNAT1 inhibition also activated PI3K/AKT signaling, promoting cell proliferation, impaired cell adhesion by mis-localizing Eph Receptor B6, enhancing migration via the RhoA (Ras homolog family member A) pathway and promoting epithelial-to-mesenchymal transition. These findings suggest that HBP plays a critical role in regulating CRPC cell behavior, and targeting this pathway could provide a novel therapeutic approach.

Indexed as

Biosynthetic PathwaysCell MovementCytoskeletonHexosaminesProstatic NeoplasmsProstatic Neoplasms, Castration-ResistantCell Line, TumorCell ProliferationGlucosamine 6-Phosphate N-AcetyltransferaseHumansMaleSignal TransductionGlucosamine 6-Phosphate N-AcetyltransferaseHexosaminesCell migrationCell proliferationCell signalingCytoskeletonHexosamine biosynthetic pathwayMetastatic prostate cancerMitosis

Identifiers

PMID41896862
PMCPMC13217896

What Socratic holds

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LicenceCC BY
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.