scholarly journals Overexpression of p75NTR in Human Seminoma: A New Biomarker?

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 629
Author(s):  
Anna Perri ◽  
Vittoria Rago ◽  
Rocco Malivindi ◽  
Lorenza Maltese ◽  
Danilo Lofaro ◽  
...  
Keyword(s):  
Human Cancer ◽  
Germ Cell Tumors ◽  
Receptor Protein ◽  
Specific Marker ◽  
Nuclear Staining ◽  
Trka Receptor ◽  
Testicular Germ Cell ◽  
Cancer Types ◽  
First Time

Several studies have demonstrated that the p75NTR low-affinity receptor of Nerve Growth Factor (NGF), is produced in abnormally large amounts in several human cancer types. However, the role of p75NTR varies substantially depending on cell context, so that a dual role of this receptor protein in tumor cell survival and invasion, as well as cell death, has been supported in recent studies. Herein we explored for the first time the expression of p75NTR in human specimens (nr = 40) from testicular germ cell tumors (TGCTs), mostly seminomas. Nuclear overexpression of p75NTR was detected by immunohistochemistry in seminoma tissue as compared to normal tissue, whereas neither NGF nor its high-affinity TrkA receptor was detected. An increased nuclear staining of phospho-JNK, belonging to the p75NTR signaling pathway and its pro-apoptotic target gene, p53, was concomitantly observed. Interestingly, our analysis revealed that decreased expression frequency of p75NTR, p-JNK and p53 was related to staging progression, thus suggesting that p75NTR may represent a specific marker for seminoma and staging in TGCTs.

scholarly journals Overexpression of p75NTR in Testicular Germ Cell Tumors: a New Biomarker of Cancer Differentiation?

2021 ◽  
Author(s):  
Anna Perri ◽  
Vittoria Rago ◽  
Rocco Malivindi ◽  
Lorenza Maltese ◽  
Danilo Lofaro ◽  
...  
Keyword(s):  
Germ Cell ◽  
Human Cancer ◽  
Germ Cell Tumors ◽  
Receptor Protein ◽  
Specific Marker ◽  
Nuclear Staining ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Cancer Types

Several studies have demonstrated that the p75NTR low-affinity receptor of Nerve Growth Factor (NGF), is produced in abnormally large amounts in several human cancer types. However, the role of p75NTR varies substantially depending on cell context, so that a dual role of this receptor protein in tumor cell survival and invasion, as well as cell death, has been supported in recent studies. Herein we explored for the first time the expression of p75NTR in human specimens (nr=40) from testicular germ cell tumors (TGCTs), mostly seminomas. Nuclear overexpression of p75NTR was detected by immunohistochemistry in tumor tissue as compared to normal tissue, whereas neither NGF nor its high-affinity TrkA receptor was detected. An increased nuclear staining of phospho-JNK, belonging to the p75NTR signaling pathway, and its pro-apoptotic target gene, p53, was concomitantly observed. Interestingly, our analysis revealed that decreased expression frequency of p75NTR, p-JNK, and p53 was related to staging progression, thus suggesting that p75NTR may represent a specific marker of differentiation in TGCTs.

Brachyury, a driver of epithelial mesenchymal transition, as an independent prognostic factor in high-grade testicular germ cell tumors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16039-e16039
Author(s):  
Flavio Mavignier Carcano ◽  
Filipe Pinto ◽  
Eduardo CA da Silva ◽  
Daniel Onofre Vidal ◽  
Cristovam Scapulatempo Neto ◽  
...  
Keyword(s):  
High Risk ◽  
Subcellular Localization ◽  
Germ Cell ◽  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Germ Cell Tumors ◽  
Specific Marker ◽  
Nuclear Staining ◽  
Testicular Germ Cell ◽  
Mesenchymal Transition

e16039 Background: The T-box transcription factor Brachyury has been considered a cancer-specific marker and a novel oncotarget in solid tumors. Brachyury overexpression has been described in various cancers, being associated with epithelial-mesenchymal transition, metastasis and poor prognosis. However, its clinical association with testicular germ cell tumor (TGCT) is unknown. Methods: We analyzed the expression of Brachyury both at protein and transcript levels in a series of 96 TGCT samples and by in silico analysis, respectively. Additionally, we investigated the clinical significance of Brachyury in TGCT. Results: Brachyury protein showed to be over-represented in 89.6% (86/96) of TGCT cases with nuclear staining in 24% (23/96) of them. Microarray expression analysis in two independent cohorts of TGCTs showed similar results with increased levels of Brachyury in TGCTs and metastasis compared with normal testis. Clinically, Brachyury nuclear staining was statistically associated with event-free survival (p = 0.04) and overall survival (p = 0.01) in intermediate/high-risk TGCTs. Multivariate analysis showed that Brachyury nuclear subcellular localization was an independent predictor of poor prognosis (HR: 3.56, p = 0.06). Conclusions: These results indicate that Brachyury plays an oncogenic role in TGCTs and its subcellular localization in the nucleus is a potential novel biomarker of poor prognosis and an oncotarget for intermediate/high-risk TGCTs treatment.

Long noncoding RNA ANRIL as a novel biomarker in human cancer

2020 ◽  
Vol 16 (35) ◽  
pp. 2981-2995
Author(s):  
Ning Lou ◽  
Guohong Liu ◽  
Yunbao Pan
Keyword(s):  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Cell Cycle Progression ◽  
Potential Role ◽  
Human Cancer ◽  
Cycle Progression ◽  
Diagnosis And Prognosis ◽  
Cancer Types ◽  
Cancer Medicine

The long noncoding RNA ANRIL, located in the human chromosome 9p21 region, has been reported to be involved in tumor progression. ANRIL regulates gene expression via recruiting PRC2 or titrating miRNA; it also participates in signaling pathways. Evidence has indicated that ANRIL is overexpressed in many cancer types and is capable of enhancing cell proliferation and cell cycle progression and inhibiting apoptosis and senescence. ANRIL has the potential to serve as a biomarker for diagnosis and prognosis in cancer. In this article we focus on recent advances in studies of the oncogenic role of ANRIL and its potential role in cancer medicine.

scholarly journals Heat Shock Proteins Are Essential Components in Transformation and Tumor Progression: Cancer Cell Intrinsic Pathways and Beyond

2019 ◽  
Vol 20 (18) ◽  
pp. 4507 ◽  
Author(s):  
Lang ◽  
Guerrero-Giménez ◽  
Prince ◽  
Ackerman ◽  
Bonorino ◽  
...  
Keyword(s):  
Heat Shock ◽  
Cancer Cells ◽  
Stress Proteins ◽  
De Novo ◽  
Human Cancer ◽  
Essential Components ◽  
Wide Range ◽  
Cancer Types ◽  
Shock Proteins

Heat shock protein (HSP) synthesis is switched on in a remarkably wide range of tumor cells, in both experimental animal systems and in human cancer, in which these proteins accumulate in high levels. In each case, elevated HSP concentrations bode ill for the patient, and are associated with a poor outlook in terms of survival in most cancer types. The significance of elevated HSPs is underpinned by their essential roles in mediating tumor cell intrinsic traits such as unscheduled cell division, escape from programmed cell death and senescence, de novo angiogenesis, and increased invasion and metastasis. An increased HSP expression thus seems essential for tumorigenesis. Perhaps of equal significance is the pronounced interplay between cancer cells and the tumor milieu, with essential roles for intracellular HSPs in the properties of the stromal cells, and their roles in programming malignant cells and in the release of HSPs from cancer cells to influence the behavior of the adjacent tumor and infiltrating the normal cells. These findings of a triple role for elevated HSP expression in tumorigenesis strongly support the targeting of HSPs in cancer, especially given the role of such stress proteins in resistance to conventional therapies.

scholarly journals The Role of the Mouse Y Chromosome on Susceptibility to Testicular Germ Cell Tumors

2009 ◽  
Vol 69 (8) ◽  
pp. 3614-3618 ◽  
Author(s):  
Philip D. Anderson ◽  
Man-Yee Lam ◽  
Christophe Poirier ◽  
Colin E. Bishop ◽  
Joseph H. Nadeau
Keyword(s):  
Germ Cell ◽  
Y Chromosome ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell

scholarly journals SPOP mutation induces replication over-firing by impairing Geminin ubiquitination and triggers replication catastrophe upon ATR inhibition

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jian Ma ◽  
Qing Shi ◽  
Gaofeng Cui ◽  
Haoyue Sheng ◽  
Maria Victoria Botuyan ◽  
...  
Keyword(s):  
Dna Replication ◽  
Ubiquitin Ligase ◽  
Genome Instability ◽  
Human Cancer ◽  
Adaptor Protein ◽  
Dna Unwinding ◽  
Binding Partner ◽  
Lysine Residues ◽  
Cancer Types

AbstractGeminin and its binding partner Cdt1 are essential for the regulation of DNA replication. Here we show that the CULLIN3 E3 ubiquitin ligase adaptor protein SPOP binds Geminin at endogenous level and regulates DNA replication. SPOP promotes K27-linked non-degradative poly-ubiquitination of Geminin at lysine residues 100 and 127. This poly-ubiquitination of Geminin prevents DNA replication over-firing by indirectly blocking the association of Cdt1 with the MCM protein complex, an interaction required for DNA unwinding and replication. SPOP is frequently mutated in certain human cancer types and implicated in tumorigenesis. We show that cancer-associated SPOP mutations impair Geminin K27-linked poly-ubiquitination and induce replication origin over-firing and re-replication. The replication stress caused by SPOP mutations triggers replication catastrophe and cell death upon ATR inhibition. Our results reveal a tumor suppressor role of SPOP in preventing DNA replication over-firing and genome instability and suggest that SPOP-mutated tumors may be susceptible to ATR inhibitor therapy.

scholarly journals Pan-cancer analysis of the oncogenic role of discs large homolog associated protein 5 (DLGAP5) in human tumors

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Neng Tang ◽  
Xiaolin Dou ◽  
Xing You ◽  
Qiman Shi ◽  
Mujing Ke ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Cellular Proliferation ◽  
Germ Cell Tumors ◽  
Enrichment Analysis ◽  
Human Tumors ◽  
Testicular Germ Cell ◽  
Pan Cancer

Abstract Background In recent years, there have been many studies on the relationship between DLGAP5 and different types of cancers, yet there is no pan-cancer analysis of DLGAP5. Therefore, this study aims to analyze the roles of DLGAP5 in human tumors. Methods Firstly, we evaluated the expression level of DLGAP5 in 33 types of tumors throughout the datasets of TCGA (Cancer Genome Atlas) and GEO (Gene Expression Synthesis). Secondly, we used the GEPIA2 and Kaplan-Meier plotter to conduct Survival prognosis analysis. Additionally, cBioPortal web was utilized to analyze the genetic alteration of DLGAP5, after which we selected hepatocellular carcinoma (HCC) cell lines to define the function of DLGAP5. Last but not least, we performed immune infiltration analysis and DLGAP5-related gene enrichment analysis. Results DLGAP5 is highly expressed in most type of cancers, and there is a significant correlation between the expression of DLGAP5 and the prognosis of cancer patients. We have observed that DLGAP5 promotes the proliferation and invasion of hepatocellular carcinoma (HCC) cell lines. We also found that DLGAP5 expression was related with the CD8+ T-cell infiltration status in kidney renal clear cell carcinoma, uveal melanoma, and thymoma, and cancer-associated fibroblast infiltration was observed in breast invasive carcinoma, kidney renal papillary cell carcinoma and testicular germ cell tumors. In addition, enrichment analysis revealed that cell cycle- and oocyte meiosis-associated functions were involved in the functional mechanism of DLGAP5. Conclusions Taken together, our unpresented pan-cancer analysis of DLGAP5 provides a relatively integrative understanding of the oncogenic role of DLGAP5 in various tumors. DLGAP5 may prompt HCC cellular proliferation, invasion and metastasis. All of these provides solid basement and will promote more advanced understanding the role of DLGAP5 in tumorigenesis and development from the perspective of clinical tumor samples and cells.

scholarly journals SGK1 in Human Cancer: Emerging Roles and Mechanisms

2021 ◽  
Vol 10 ◽  
Author(s):  
Yiwen Sang ◽  
Piaoping Kong ◽  
Shizhen Zhang ◽  
Lingyu Zhang ◽  
Ying Cao ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Kinase Activity ◽  
Human Cancer ◽  
Therapy Resistance ◽  
Cancer Cell Proliferation ◽  
Serine Threonine Kinase ◽  
Aberrant Expression ◽  
Threonine Kinase ◽  
Cancer Types

Serum and glucocorticoid-induced protein kinase 1 (SGK1) is a member of the “AGC” subfamily of protein kinases, which shares structural and functional similarities with the AKT family of kinases and displays serine/threonine kinase activity. Aberrant expression of SGK1 has profound cellular consequences and is closely correlated with human cancer. SGK1 is considered a canonical factor affecting the expression and signal transduction of multiple genes involved in the genesis and development of many human cancers. Abnormal expression of SGK1 has been found in tissue and may hopefully become a useful indicator of cancer progression. In addition, SGK1 acts as a prognostic factor for cancer patient survival. This review systematically summarizes and discusses the role of SGK1 as a diagnostic and prognostic biomarker of diverse cancer types; focuses on its essential roles and functions in tumorigenesis, cancer cell proliferation, apoptosis, invasion, metastasis, autophagy, metabolism, and therapy resistance and in the tumor microenvironment; and finally summarizes the current understanding of the regulatory mechanisms of SGK1 at the molecular level. Taken together, this evidence highlights the crucial role of SGK1 in tumorigenesis and cancer progression, revealing why it has emerged as a potential target for cancer therapy.

scholarly journals Role of microRNAs in mammalian spermatogenesis and testicular germ cell tumors

Reproduction ◽  
2015 ◽  
Vol 149 (3) ◽  
pp. R127-R137 ◽  
Author(s):  
Li Wang ◽  
Chen Xu
Keyword(s):  
Germ Cell ◽  
Expression Profiles ◽  
Regulation Of Gene Expression ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumors ◽  
Mirna Regulation ◽  
Testicular Germ Cell ◽  
Complex Process ◽  
Regulatory Functions

microRNAs (miRNAs) are a class of small endogenous RNAs, 19–25 nucleotides in size, which play a role in the regulation of gene expression at transcriptional and post-transcriptional levels. Spermatogenesis is a complex process through which spermatogonial stem cells (SSCs) proliferate and differentiate into mature spermatozoa. A large number of miRNAs are abundantly expressed in spermatogenic cells. Growing evidence supports the essential role of miRNA regulation in normal spermatogenesis and male fertility and cumulative research has shown that this form of regulation contributes to the etiology of testicular germ cell tumors (TGCTs). In this review, we addressed recent advancements of miRNA expression profiles in testis and focused on the regulatory functions of miRNA in the process of SSC renewal, spermatogonial mitosis, spermatocyte meiosis, spermiogenesis, and the occurrence of TGCTs.

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