<i>AXIN2</i>
 expression predicts prostate cancer recurrence and regulates invasion and tumor growth

Hu, Brian; Fairey, Adrian; Madhav, Anisha; Yang, Dongyun; Li, Meng; Groshen, Susan; Stephens, Craig; Kim, Philip H.; Virk, Navneet; Wang, Lina; Martin, Sue Ellen; Erho, Nicholas; Davicioni, Elai; Jenkins, Robert B.; Den, Robert B.; Xu, Tong; Xu, Yang; Gill, Inderbir S.; Quinn, David I.; Goldkorn, Amir

doi:10.1002/pros.23151

Cited by 14 publications

(11 citation statements)

References 50 publications

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“…Decreased expression of AXIN2 is associated with cellular invasion and proliferation as well poor prognosis in prostate cancer and regulation of cMYC pathway members (33,34). Changes in the expression of TGF-β2 (Transforming growth factor beta 2) are also implicated in prostate cancer progression (35,36).…”

Section: Resultsmentioning

confidence: 99%

MEIS1 and MEIS2 Expression and Prostate Cancer Progression: A Role For HOXB13 Binding Partners in Metastatic Disease

Bhanvadia

VanOpstall

Brechka

et al. 2018

Clinical Cancer Research

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Germline mutations within the MEIS-interaction domain of HOXB13 have implicated a critical function for MEIS-HOX interactions in prostate cancer etiology and progression. The functional and predictive role of changes in MEIS expression within prostate tumor progression, however, remain largely unexplored. Here we utilize RNA expression datasets, annotated tissue microarrays, and cell-based functional assays to investigate the role of MEIS1 and MEIS2 in prostate cancer and metastatic progression. These analyses demonstrate a stepwise decrease in the expression of both MEIS1 and MEIS2 from benign epithelia, to primary tumor, to metastatic tissues. Positive expression of MEIS proteins in primary tumors, however, is associated with a lower hazard of clinical metastasis (HR = 0.28) after multivariable analysis. Pathway and gene set enrichment analyses identified MEIS-associated networks involved in cMYC signaling, cellular proliferation, motility, and local tumor environment. Depletion of MEIS1 and MEIS2 resulted in increased tumor growth over time , and decreased MEIS expression in both patient-derived tumors and MEIS-depleted cell lines was associated with increased expression of the protumorigenic genes cMYC and CD142, and decreased expression of AXIN2, FN1, ROCK1, SERPINE2, SNAI2, and TGFβ2. These data implicate a functional role for MEIS proteins in regulating cancer progression, and support a hypothesis whereby tumor expression of MEIS1 and MEIS2 expression confers a more indolent prostate cancer phenotype, with a decreased propensity for metastatic progression. .

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Section: Resultsmentioning

confidence: 99%

MEIS1 and MEIS2 Expression and Prostate Cancer Progression: A Role For HOXB13 Binding Partners in Metastatic Disease

Bhanvadia

VanOpstall

Brechka

et al. 2018

Clinical Cancer Research

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“…The single nucleotide polymorphism (guanine/adenine) rs2240308 is associated with a decrease in the risk of PC (OR, 0.377; 95% CI, 0.206-0.688; P= 0.001) (85). Of note, the downregulation of AXIN2 mRNA expression has been found to be a risk factor of BCR (Table II) (86).…”

Section: Gene Expression-based Biomarkersmentioning

confidence: 99%

Assessment of biochemical recurrence of prostate cancer (Review)

Lin

Kapoor

et al. 2019

Int J Oncol

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The assessment of the risk of biochemical recurrence (BCR) is critical in the management of males with prostate cancer (PC). Over the past decades, a comprehensive effort has been focusing on improving risk stratification; a variety of models have been constructed using PC-associated pathological features and molecular alterations occurring at the genome, protein and RNA level. Alterations in RNA expression (lncRNA, miRNA and mRNA) constitute the largest proportion of the biomarkers of BCR. In this article, we systemically review RNA-based BCR biomarkers reported in PubMed according to the PRISMA guidelines. Individual miRNAs, mRNAs, lncRNAs and multigene panels, including the commercially available signatures, Oncotype DX and Prolaris, will be discussed; details related to cohort size, hazard ratio and 95% confidence intervals will be provided. Mechanistically, these individual biomarkers affect multiple pathways critical to tumorigenesis and progression, including epithelial-mesenchymal transition (EMT), phosphatase and tensin homolog (PTEN), Wnt, growth factor receptor, cell proliferation, immune checkpoints and others. This variety in the mechanisms involved not only validates their associations with BCR, but also highlights the need for the coverage of multiple pathways in order to effectively stratify the risk of BCR. Updates of novel biomarkers and their mechanistic insights are considered, which suggests new avenues to pursue in the prediction of BCR. Additionally, the management of patients with BCR and the potential utility of the stratification of the risk of BCR in salvage treatment decision making for these patients are briefly covered. Limitations will also be discussed. Contents 1. Introduction 2. Stratification of BCR risk: An update 3. Searching methods for RNA-based BCR biomarkers 4. Gene expression-based biomarkers 5. Management of patients with biochemical recurrence 6. Perspectives

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“…During embryonic and postnatal development, WNT signaling controls many cellular processes, including proliferation, survival and differentiation [ 22 , 23 , 24 , 25 , 26 ]. Deregulation in WNT signaling leads to an imbalance of such processes, often resulting in aberrant development or disease [ 27 , 28 ]; in particular, deregulated WNT signaling is common in human cancers, including malignancies of the intestine [ 29 , 30 , 31 ], liver [ 32 , 33 , 34 , 35 ], skin [ 36 , 37 ], breast [ 38 , 39 , 40 , 41 ] and prostate [ 42 , 43 ].…”

Section: Introductionmentioning

confidence: 99%

A Tale of Two Signals: AR and WNT in Development and Tumorigenesis of Prostate and Mammary Gland

Pakula

Xiang

2017

Cancers

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Prostate cancer (PCa) is one of the most common cancers and among the leading causes of cancer deaths for men in industrialized countries. It has long been recognized that the prostate is an androgen-dependent organ and PCa is an androgen-dependent disease. Androgen action is mediated by the androgen receptor (AR). Androgen deprivation therapy (ADT) is the standard treatment for metastatic PCa. However, almost all advanced PCa cases progress to castration-resistant prostate cancer (CRPC) after a period of ADT. A variety of mechanisms of progression from androgen-dependent PCa to CRPC under ADT have been postulated, but it remains largely unclear as to when and how castration resistance arises within prostate tumors. In addition, AR signaling may be modulated by extracellular factors among which are the cysteine-rich glycoproteins WNTs. The WNTs are capable of signaling through several pathways, the best-characterized being the canonical WNT/β-catenin/TCF-mediated canonical pathway. Recent studies from sequencing PCa genomes revealed that CRPC cells frequently harbor mutations in major components of the WNT/β-catenin pathway. Moreover, the finding of an interaction between β-catenin and AR suggests a possible mechanism of cross talk between WNT and androgen/AR signaling pathways. In this review, we discuss the current knowledge of both AR and WNT pathways in prostate development and tumorigenesis, and their interaction during development of CRPC. We also review the possible therapeutic application of drugs that target both AR and WNT/β-catenin pathways. Finally, we extend our review of AR and WNT signaling to the mammary gland system and breast cancer. We highlight that the role of AR signaling and its interaction with WNT signaling in these two hormone-related cancer types are highly context-dependent.

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AXIN2 expression predicts prostate cancer recurrence and regulates invasion and tumor growth

Cited by 14 publications

References 50 publications

MEIS1 and MEIS2 Expression and Prostate Cancer Progression: A Role For HOXB13 Binding Partners in Metastatic Disease

MEIS1 and MEIS2 Expression and Prostate Cancer Progression: A Role For HOXB13 Binding Partners in Metastatic Disease

Assessment of biochemical recurrence of prostate cancer (Review)

A Tale of Two Signals: AR and WNT in Development and Tumorigenesis of Prostate and Mammary Gland

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