Evidence map›Paper›PMID 40626835›Full record

ArticleCancer biology & medicine2025

The polarity protein Par3 enhances renal cell carcinoma metastasis

Soo Lee, Jonathan Balcazar, Karla Davis, Rey-Chen Pong, Jer-Tsong Hsieh, Payal Kapur, Xiaosong Meng

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Article in Cancer biology & medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Soo LeeDepartment of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Jonathan BalcazarDepartment of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Karla DavisDepartment of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Rey-Chen PongDepartment of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Jer-Tsong HsiehDepartment of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Payal KapurDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Xiaosong MengDepartment of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.ORCID 0000-0003-1120-7691

Funding

UT Southwestern Medical Center Simmons Comprehensive Cancer CenterP30CA142543 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Kathryn Ann O'Donnell · 2010 to 2026
$53.7M
NCI NIH HHS P30 CA142543
6 · The paper itself

Abstract

objectivePartitioning defective protein 3 (Par3) has recently been found to have important roles in cancer progression. Interestingly, Par3's functions vary among cancers: both Par3 elevation (in the prostate or liver) and loss (in the breast or lung) have been implicated in cancer metastasis. Although Par3 overexpression has been correlated with diminished survival in renal cell carcinoma (RCC), data indicating the role of Par3 in RCC metastasis are lacking. Given reports of interactions between Par3 and oncoproteins such as Yes-associated protein (YAP)/WW domain-containing transcription regulator 1 (TAZ), we investigated whether Par3-mediated RCC metastasis might be due to activation of the Hippo pathway components YAP and TAZ.

methodsPar3 levels were analyzed in RCC cell lines and human RCC patient tissues by western blotting and immunohistochemical (IHC) staining, as appropriate. Co-immunoprecipitation (co-IP) and immunofluorescence studies were conducted to examine the interaction between Par3 and YAP. Quantitative PCR and luciferase assays were used to investigate the effects of Par3 on YAP target gene expression and co-transcriptional regulation. PDZ domain deletion mutants of Par3 were generated to elucidate the structural basis of the interaction between Par3 and YAP.

resultsHigher Par3 levels were found in distant-organ-RCC-metastasis-derived ACHN sublines than wild type ACHN cell lines. Par3 levels were also higher in the patient tissue obtained from metastatic sites than in normal kidney and primary RCC tumor tissues. Co-IP and IHC experiments demonstrated that Par3 directly interacted and co-localized with YAP/TAZ proteins. Moreover, Par3 upregulated the transcription of YAP/TAZ downstream target genes and increased the luciferase activity of YAP/TAZ responsive elements. PDZ domain 3 in the

conclusionsTogether, these results indicate the role of Par3 in RCC metastasis,

Indexed as

Adaptor Proteins, Signal TransducingCarcinoma, Renal CellCell Cycle ProteinsKidney NeoplasmsMembrane ProteinsTranscription FactorsAcyltransferasesCell Line, TumorGene Expression Regulation, NeoplasticHumansNeoplasm MetastasisSignal TransductionTrans-ActivatorsTranscriptional Coactivator with PDZ-Binding Motif ProteinsYAP-Signaling ProteinsAcyltransferasesAdaptor Proteins, Signal TransducingCell Cycle ProteinsMembrane ProteinsPARD3 protein, humanTrans-ActivatorsTranscriptional Coactivator with PDZ-Binding Motif ProteinsTranscription FactorsWWTR1 protein, humanYAP1 protein, humanYAP-Signaling ProteinsmetastasisPar3Renal cell carcinoma (RCC)YAP

Identifiers

PMID40626835
PMCPMC12302271

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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.