<i>MAP3K7</i> Loss Drives Enhanced Androgen Signaling and Independently Confers Risk of Recurrence in Prostate Cancer with Joint Loss of <i>CHD1</i>

Jillson, Lauren K.; Rider, Leah; Rodrigues, Lindsey Ulkus; Romero, Lina; Karimpour-Fard, Anis; Nieto, Cera; Gillette, Claire; Torkko, Kathleen C.; Danis, Etienne; Smith, Elizabeth E.; Nolley, Rosalie; Peehl, Donna M.; Lucia, M. Scott; Costello, James C.; Cramer, Scott D.

doi:10.1158/1541-7786.mcr-20-0913

Cited by 11 publications

(25 citation statements)

References 51 publications

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“…A putative mechanism of AR regulation by MAP kinases is direct phosphorylation, but a link between AR phosphorylation and MAP3K7 loss has not been identified [47,48]. Our previous study demonstrated that MAP3K7 loss, when co-lost with CHD1, is associated with increased AR activity [45]. Our meta-analysis supports these initial findings.…”

Section: Map3k7supporting

confidence: 81%

“…Recent studies have discovered that loss of CHD1 affects the distribution of AR chromatin binding. Many loci are differentially or newly bound by AR, resulting in more oncogenic expression profiles [45,52]. In concordance with its effects on AR chromatin distribution, patients with CHD1 loss exhibited higher than average AR scores, but not AR mRNA levels in our meta-analysis (Figure 2a,b).…”

Section: Chd1supporting

confidence: 70%

“…MAP3K7 is a member of the greater MAP kinase family that signals downstream to p38, JNK, and NF-kB, and is a bona fide tumor suppressor in PCa [41]. MAP3K7 loss is sufficient for initiating precancerous and cancerous lesions in tissue recombination mouse models, is associated with high-grade PCa, and is linked to biochemical recurrence and prostatic brain metastases [42][43][44][45][46].…”

Section: Map3k7mentioning

confidence: 99%

“…Present on chromosome 5q, CHD1 is deleted in 17-18% of primary PCa (Figure 1). While CHD1 loss is not sufficient alone for tumorigenesis in mouse models, it is a PCa tumor suppressor and cooperates with other genomic alterations to drive disease progression [42,45,52]. While no direct interaction has been identified between AR and CHD1, the CHD1 interactome does involve nuclear receptor cofactors [52].…”

Section: Chd1mentioning

confidence: 99%

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Androgen Receptor Signaling in Prostate Cancer Genomic Subtypes

Jillson

Yette

Laajala

et al. 2021

Cancers

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While many prostate cancer (PCa) cases remain indolent and treatable, others are aggressive and progress to the metastatic stage where there are limited curative therapies. Androgen receptor (AR) signaling remains an important pathway for proliferative and survival programs in PCa, making disruption of AR signaling a viable therapy option. However, most patients develop resistance to AR-targeted therapies or inherently never respond. The field has turned to PCa genomics to aid in stratifying high risk patients, and to better understand the mechanisms driving aggressive PCa and therapy resistance. While alterations to the AR gene itself occur at later stages, genomic changes at the primary stage can affect the AR axis and impact response to AR-directed therapies. Here, we review common genomic alterations in primary PCa and their influence on AR function and activity. Through a meta-analysis of multiple independent primary PCa databases, we also identified subtypes of significantly co-occurring alterations and examined their combinatorial effects on the AR axis. Further, we discussed the subsequent implications for response to AR-targeted therapies and other treatments. We identified multiple primary PCa genomic subtypes, and given their differing effects on AR activity, patient tumor genetics may be an important stratifying factor for AR therapy resistance.

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Section: Map3k7supporting

confidence: 81%

Section: Chd1supporting

confidence: 70%

Section: Map3k7mentioning

confidence: 99%

Section: Chd1mentioning

confidence: 99%

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Androgen Receptor Signaling in Prostate Cancer Genomic Subtypes

Jillson

Yette

Laajala

et al. 2021

Cancers

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“…Biomarkers' "smart" manipulation was thought also to block the PCa recurrence after various types of treatments (e.g. [8,9].…”

Section: Introductionmentioning

confidence: 99%

Personalized 1-2-3-Gene(s) Tickets to Cancer-Free Prostate

Iacobaş¹,

Iacobaş²

2021

Preprint

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Many years and $$$ spent for research did not yet produced a universally effective gene therapy of prostate cancer (PCa). Our studies indicated that not only each human, but even each cancer nodule in the same tumor has unique and dynamic gene expression profile, control and coordination. The tumor heterogeneity of the transcriptome topology is a strong argument in favor of personalized gene therapies, tailored on patients’ primary tumor unique characteristics. Here, we propose a bioinformatics procedure by which to identify the Gene Master Regulators (GMR) of cancer cells from transcriptomic data and predict consequences of their experimental manipulation. The procedure, based on our Genomic Fabric Paradigm (GFP), can determine the most important gene in each cancer nodule whose controlled alteration would selectively kill the cancer cells. In this report, the method is applied to our microarray data on two men PCs (each with three distinct cancer nodules) and two standard human PCa cell lines (DU145 and LNCaP). We expect the industry to produce ready-to-use CRISPR constructs for all genes allowing the clinical oncologist to prescribe the adequate personalized CRISPR cocktail for his/her patient. Thus, the GMR approach may provide the most effective, yet affordable solution in fighting cancer.

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Unveiling NRlncRNAs as prognostic biomarkers and therapeutic targets for head‐and‐neck squamous cell carcinoma through machine learning

Shao,

Xiong,

Lei

et al. 2024

Environmental Toxicology

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Head‐and‐neck squamous cell carcinoma (HNSCC) patients often exhibit insensitivity to immunotherapy, leading to treatment failure. Identifying potential biomarkers that can predict prognosis and improve the efficacy of treatment is crucial. In this study, we aimed to identify necroptosis‐related long noncoding RNAs (NRlncRNAs) as potential therapeutic targets to improve the prognosis of HNSCC patients. By exploring the Genotype‐Tissue Expression Project (GTEx) and the Cancer Genome Atlas (TCGA) databases, we identified NRlncRNAs and developed a risk model comprising 17 NRlncRNAs to predict the prognosis of HNSCC patients and to classify patients into two clusters based on their expression levels. We conducted various analyses, such as the Kaplan–Meier analysis, GSEA and IC50 prediction, to evaluate the differences in sensitivity to immunotherapy between the two clusters. Our findings suggest that NRlncRNAs have potential as therapeutic targets for improving the prognosis of HNSCC patients, and that individualized treatment approaches based on NRlncRNA expression levels can improve the sensitivity of immunotherapy and overall treatment outcomes. This study highlights new perspectives within clinical cancer informatics and provides insight into potential therapeutic strategies for HNSCC patients.

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MAP3K7 Loss Drives Enhanced Androgen Signaling and Independently Confers Risk of Recurrence in Prostate Cancer with Joint Loss of CHD1

Cited by 11 publications

References 51 publications

Androgen Receptor Signaling in Prostate Cancer Genomic Subtypes

Androgen Receptor Signaling in Prostate Cancer Genomic Subtypes

Personalized 1-2-3-Gene(s) Tickets to Cancer-Free Prostate

Unveiling NRlncRNAs as prognostic biomarkers and therapeutic targets for head‐and‐neck squamous cell carcinoma through machine learning

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