scholarly journals m6A Methylation Regulators Are Predictive Biomarkers for Tumour Metastasis in Prostate Cancer

2020 ◽  
Author(s):  
Xiaobo Wu ◽  
Qianwen Ge ◽  
Chen Yang ◽  
Yishuo Wu ◽  
Mengbo Hu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Consensus Clustering ◽  
Prostate Cancer Progression ◽  
Prostate Cancer Metastasis ◽  
Prostate Cancers

Abstract BackgroundProstate cancer is one of the most common cancers in men. Usually, most prostate cancers are localized in initial diagnoses and grow slowly. Patients with localized prostate cancers have a nearly 100% 5-year survival rate; however, the 5-year survival rate of metastatic or progressive prostate cancer is still dismal. N6-methyladenosine (m6A) is the most common post-transcriptional mRNA modification and is dynamically regulated by m6A regulators. A few studies have shown that the abnormal expression of m6A regulators is significantly associated with cancer progression and immune cell infiltration, but the roles of these regulators in prostate cancer remain unclear. MethodsHere, we comprehensively examined the patterns of 21 m6A regulators across 494 prostate cancers and systematically correlated m6A regulators with prostate cancer progression and immune cell infiltration. Consensus clustering was utilized for the subtype identification of m6A regulators for prostate cancers. Each subtype signature genes were obtained by the pairwise differentially expressed genes. Featured pathways of m6A subtypes were predicted consequently. The m6A score was constructed to predict the m6A activation. The association of m6A score with patients’ survival, metastasis and immune cell infiltration were also investigated. ResultsWe identified three distinct clusters in prostate cancer based on the expression profiles of 21 m6A regulators by consensus clustering. The differential expression and pathway analyses on the three clusters uncovered the m6A regulators involved in metabolic processes and immune responses in prostate cancer. Moreover, we established an m6A score to perceive the m6A regulator activation for prostate cancer. The m6A score is significantly associated with Gleason scores and metastasis in prostate cancer. The predictive capacity of m6A score on prostate cancer metastasis was also validated in another independent cohort. ConclusionOur study revealed the critical role of m6A regulators in prostate cancer progression and m6A score is promising predictive biomarker for prostate cancer metastasis.

scholarly journals RIPK2 Stabilizes c-Myc and is an Actionable Target for Inhibiting Prostate Cancer Metastasis

2020 ◽  
Author(s):  
Yiwu Yan ◽  
Bo Zhou ◽  
Chen Qian ◽  
Alex Vasquez ◽  
Avradip Chatterjee ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Drug Targets ◽  
Cancer Metastasis ◽  
Therapeutic Interventions ◽  
Interacting Protein ◽  
Prostate Cancer Metastasis ◽  
Prostate Cancers

AbstractDespite advances in diagnosis and treatment, metastatic prostate cancer remains incurable and is associated with high mortality rates. Thus, novel actionable drug targets are urgently needed for therapeutic interventions in advanced prostate cancer. Here we report receptor-interacting protein kinase 2 (RIPK2) as an actionable drug target for suppressing prostate cancer metastasis. RIPK2 is frequently amplified in lethal prostate cancers and its overexpression is associated with disease progression and aggressiveness. Genetic and pharmacological inhibition of RIPK2 significantly suppressed prostate cancer progression in vitro and metastasis in vivo. Multi-level proteomic analysis revealed that RIPK2 strongly regulates c-Myc protein stability and activity, largely by activating the MKK7/JNK/c-Myc phosphorylation pathway—a novel, non-canonical RIPK2 signaling pathway. Targeting RIPK2 inhibits this phosphorylation pathway, and thus promotes the degradation of c-Myc—a potent oncoprotein for which no drugs have been approved for clinical use yet. These results support targeting RIPK2 for personalized therapy in prostate cancer patients towards improving survival.

scholarly journals EphA6 promotes angiogenesis and prostate cancer metastasis and is associated with human prostate cancer progression

Oncotarget ◽  
2015 ◽  
Vol 6 (26) ◽  
pp. 22587-22597 ◽  
Author(s):  
Shibao Li ◽  
Yingyu Ma ◽  
Chongwei Xie ◽  
Zhiyuan Wu ◽  
Zhihua Kang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Progression ◽  
Prostate Cancer Metastasis

scholarly journals Role of Exosomes in Prostate Cancer Metastasis

2021 ◽  
Vol 22 (7) ◽  
pp. 3528
Author(s):  
Theresa Akoto ◽  
Sharanjot Saini
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Intercellular Communication ◽  
Cancer Metastasis ◽  
Disseminated Tumor Cells ◽  
Bilayer Membrane ◽  
Prostate Cancer Progression ◽  
Prostate Cancer Metastasis

Prostate cancer remains a life-threatening disease among men worldwide. The majority of PCa-related mortality results from metastatic disease that is characterized by metastasis of prostate tumor cells to various distant organs, such as lung, liver, and bone. Bone metastasis is most common in prostate cancer with osteoblastic and osteolytic lesions. The precise mechanisms underlying PCa metastasis are still being delineated. Intercellular communication is a key feature underlying prostate cancer progression and metastasis. There exists local signaling between prostate cancer cells and cells within the primary tumor microenvironment (TME), in addition to long range signaling wherein tumor cells communicate with sites of future metastases to promote the formation of pre-metastatic niches (PMN) to augment the growth of disseminated tumor cells upon metastasis. Over the last decade, exosomes/ extracellular vesicles have been demonstrated to be involved in such signaling. Exosomes are nanosized extracellular vesicles (EVs), between 30 and 150 nm in thickness, that originate and are released from cells after multivesicular bodies (MVB) fuse with the plasma membrane. These vesicles consist of lipid bilayer membrane enclosing a cargo of biomolecules, including proteins, lipids, RNA, and DNA. Exosomes mediate intercellular communication by transferring their cargo to recipient cells to modulate target cellular functions. In this review, we discuss the contribution of exosomes/extracellular vesicles in prostate cancer progression, in pre-metastatic niche establishment, and in organ-specific metastases. In addition, we briefly discuss the clinical significance of exosomes as biomarkers and therapeutic agents.

scholarly journals Identification of immune-based prostate cancer subtypes using mRNA expression

2020 ◽  
Author(s):  
Jukun Song ◽  
Song He ◽  
Wei Wang ◽  
Jiaming Su ◽  
Dongbo Yuan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Immune Response ◽  
Immune Cells ◽  
Immune Cell ◽  
Molecular Classification ◽  
Cell Types ◽  
Functional Enrichment ◽  
Cell Infiltration ◽  
Cell Subpopulation ◽  
Immune Cell Infiltration

Abstract Background Immune infiltration of Prostate cancer (PCa) was highly related to clinical outcomes. However, previous works failed to elucidate the diversity of different immune cell types that make up the function of the immune response system. The aim of the study was to uncover the composition of TIICs in PCa utilizing the CIBERSORT algorithm and further reveal the molecular characteristics of PCa subtypes. Method In the present work, we employed the CIBERSORT method to evaluate the relative proportions of immune cell profiling in PCa and adjacent samples, normal samples. We analyzed the correlation between immune cell infiltration and clinical information. The tumor-infiltrating immune cells of the TCGA PCa cohort were analyzed for the first time. The fractions of 22 immune cell types were imputed to determine the correlation between each immune cell subpopulation and clinical feature. Three types of molecular classification were identified via R-package of “CancerSubtypes”. The functional enrichment was analyzed in each subtype. The submap and TIDE algorithm were used to predict the clinical response to immune checkpoint blockade, and GDSC was employed to screen chemotherapeutic targets for the potential treatment of PCa. Results In current work, we utilized the CIBERSORT algorithm to assess the relative proportions of immune cell profiling in PCa and adjacent samples, normal samples. We investigated the correlation between immune cell infiltration and clinical data. The tumor-infiltrating immune cells in the TCGA PCa cohort were analyzed. The 22 immune cells were also calculated to determine the correlation between each immune cell subpopulation and survival and response to chemotherapy. Three types of molecular classification were identified. Each subtype has specific molecular and clinical characteristics. Meanwhile, Cluster I is defined as advanced PCa, and is more likely to respond to immunotherapy. Conclusions Our results demonstrated that differences in immune response may be important drivers of PCa progression and response to treatment. The deconvolution algorithm of gene expression microarray data by CIBERSOFT provides useful information about the immune cell composition of PCa patients. In addition, we have found a subtype of immunopositive PCa subtype and will help to explore the reasons for the poor effect of PCa on immunotherapy, and it is expected that immunotherapy will be used to guide the individualized management and treatment of PCa patients.

Characterization of the intra-prostatic immune cell infiltration in androgen-deprived prostate cancer patients

2009 ◽  
Vol 348 (1-2) ◽  
pp. 9-17 ◽  
Author(s):  
Philippe O. Gannon ◽  
Alexis O. Poisson ◽  
Nathalie Delvoye ◽  
Réjean Lapointe ◽  
Anne-Marie Mes-Masson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Immune Cell ◽  
Cell Infiltration ◽  
Immune Cell Infiltration

scholarly journals Activation of the RalGEF/Ral Pathway Promotes Prostate Cancer Metastasis to Bone

2007 ◽  
Vol 27 (21) ◽  
pp. 7538-7550 ◽  
Author(s):  
JuanJuan Yin ◽  
Claire Pollock ◽  
Kirsten Tracy ◽  
Monika Chock ◽  
Philip Martin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Signaling Pathways ◽  
Cell Line ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Receptor Activation ◽  
Organ Specificity ◽  
Tyrosine Kinase Receptor ◽  
Nucleotide Exchange ◽  
Prostate Cancer Metastasis

ABSTRACT A hallmark of metastasis is organ specificity; however, little is known about the underlying signaling pathways responsible for the colonization and growth of tumor cells in target organs. Since tyrosine kinase receptor activation is frequently associated with prostate cancer progression, we have investigated the role of a common signaling intermediary, activated Ras, in prostate cancer metastasis. Three effector pathways downstream of Ras, Raf/extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase, and Ral guanine nucleotide exchange factors (RalGEFs), were assayed for their ability to promote the metastasis of a tumorigenic, nonmetastatic human prostate cancer cell line, DU145. Oncogenic Ras promoted the metastasis of DU145 to multiple organs, including bone and brain. Activation of the Raf/ERK pathway stimulated metastatic colonization of the brain, while activation of the RalGEF pathway led to bone metastases, the most common organ site for prostate cancer metastasis. In addition, loss of RalA in the metastatic PC3 cell line inhibited bone metastasis but did not affect subcutaneous tumor growth. Loss of Ral appeared to suppress expansive growth of prostate cancer cells in bone, whereas homing and initial colonization were less affected. These data extend our understanding of the functional roles of the Ral pathway and begin to identify signaling pathways relevant for organ-specific metastasis.

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