scholarly journals Oncogenic role of sFRP2 in P53-mutant osteosarcoma development via autocrine and paracrine mechanism

2018 ◽  
Author(s):  
Huen Suk Kim ◽  
Seungyeul Yoo ◽  
Jeffrey M. Bernitz ◽  
Ye Yuan ◽  
Andreia M. Gomes ◽  
...  
Keyword(s):  
Survival Rates ◽  
P53 Mutation ◽  
Poor Survival ◽  
Independent Manner ◽  
Li Fraumeni Syndrome ◽  
Primary Bone Tumor ◽  
Tumorigenic Potential ◽  
Normal Osteoblast ◽  
Induced Pluripotent

AbstractOsteosarcoma (OS), the most common primary bone tumor, is highly metastatic with high chemotherapeutic resistance and poor survival rates. Using induced pluripotent stem cells (iPSCs) generated from Li-Fraumeni syndrome (LFS) patients, we investigated an oncogenic role of secreted frizzled-related protein 2 (sFRP2) in P53 mutation-associated OS development. Interestingly, we found that high sFRP2 expression in OS patient samples correlates with poor survival. Systems-level analyses identified that expression of sFRP2 increases during LFS OS development and can induce angiogenesis. Ectopic sFRP2 overexpression in normal osteoblast precursors is sufficient to suppress normal osteoblast differentiation and to promote OS phenotypes through induction of oncogenic molecules such as FOXM1 and CYR61 in a β-catenin independent manner. Conversely, inhibition of sFRP2, FOXM1 or CYR61 represses the tumorigenic potential. In summary, these findings demonstrate the oncogenic role of sFRP2 in P53 mutation-associated OS development and that inhibition of sFRP2 is a potential therapeutic strategy.

scholarly journals Oncogenic role of SFRP2 in p53-mutant osteosarcoma development via autocrine and paracrine mechanism

2018 ◽  
Vol 115 (47) ◽  
pp. E11128-E11137 ◽  
Author(s):  
Huensuk Kim ◽  
Seungyeul Yoo ◽  
Ruoji Zhou ◽  
An Xu ◽  
Jeffrey M. Bernitz ◽  
...  
Keyword(s):  
Survival Rates ◽  
P53 Mutation ◽  
Poor Survival ◽  
Independent Manner ◽  
Li Fraumeni Syndrome ◽  
Primary Bone Tumor ◽  
Tumorigenic Potential ◽  
Normal Osteoblast ◽  
Induced Pluripotent

Osteosarcoma (OS), the most common primary bone tumor, is highly metastatic with high chemotherapeutic resistance and poor survival rates. Using induced pluripotent stem cells (iPSCs) generated from Li–Fraumeni syndrome (LFS) patients, we investigate an oncogenic role of secreted frizzled-related protein 2 (SFRP2) in p53 mutation-associated OS development. Interestingly, we find that high SFRP2 expression in OS patient samples correlates with poor survival. Systems-level analyses identified that expression of SFRP2 increases during LFS OS development and can induce angiogenesis. Ectopic SFRP2 overexpression in normal osteoblast precursors is sufficient to suppress normal osteoblast differentiation and to promote OS phenotypes through induction of oncogenic molecules such as FOXM1 and CYR61 in a β-catenin–independent manner. Conversely, inhibition of SFRP2, FOXM1, or CYR61 represses the tumorigenic potential. In summary, these findings demonstrate the oncogenic role of SFRP2 in the development of p53 mutation-associated OS and that inhibition of SFRP2 is a potential therapeutic strategy.

scholarly journals Therapeutically Significant MicroRNAs in Primary and Metastatic Brain Malignancies

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2534 ◽  
Author(s):  
Akilandeswari A. Balachandran ◽  
Leon M. Larcher ◽  
Suxiang Chen ◽  
Rakesh N. Veedu
Keyword(s):  
Brain Tumors ◽  
High Mortality ◽  
Survival Rates ◽  
Primary Brain Tumor ◽  
Metastatic Brain Tumors ◽  
Poor Survival ◽  
Aggressive Form ◽  
Targeted Treatments ◽  
The Given

Brain cancer is one among the rare cancers with high mortality rate that affects both children and adults. The most aggressive form of primary brain tumor is glioblastoma. Secondary brain tumors most commonly metastasize from primary cancers of lung, breast, or melanoma. The five-year survival of primary and secondary brain tumors is 34% and 2.4%, respectively. Owing to poor prognosis, tumor heterogeneity, increased tumor relapse, and resistance to therapies, brain cancers have high mortality and poor survival rates compared to other cancers. Early diagnosis, effective targeted treatments, and improved prognosis have the potential to increase the survival rate of patients with primary and secondary brain malignancies. MicroRNAs (miRNAs) are short noncoding RNAs of approximately 18–22 nucleotides that play a significant role in the regulation of multiple genes. With growing interest in the development of miRNA-based therapeutics, it is crucial to understand the differential role of these miRNAs in the given cancer scenario. This review focuses on the differential expression of ten miRNAs (miR-145, miR-31, miR-451, miR-19a, miR-143, miR-125b, miR-328, miR-210, miR-146a, and miR-126) in glioblastoma and brain metastasis. These miRNAs are highly dysregulated in both primary and metastatic brain tumors, which necessitates a better understanding of their role in these cancers. In the context of the tumor microenvironment and the expression of different genes, these miRNAs possess both oncogenic and/or tumor-suppressive roles within the same cancer.

scholarly journals USP1 Promotes GC Metastasis via Stabilizing ID2

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Nuoya Li ◽  
Lei Wu ◽  
Xingye Zuo ◽  
Huilong Luo ◽  
Yanling Sheng ◽  
...  
Keyword(s):  
Malignant Tumors ◽  
Survival Rates ◽  
Underlying Mechanism ◽  
Poor Survival ◽  
Cellular Analysis ◽  
Potential Biomarker ◽  
Therapy Target

Gastric cancer (GC) is one of the most common malignant tumors all over the world. And recurrence and metastasis are still the main causes of low survival rate for advanced GC. USP1 has been shown overexpressed in multiple cancers, which indicate its important biomarker in tumorigenesis and development. Our study is aimed at defining the exact role of USP1 on GC metastasis and the underlying mechanism. USP1 was firstly found overexpressed in GC tissues and relatively high-expression levels conferred poor survival rates. Then, real-time cellular analysis (RTCA) showed that USP1 knockdown inhibited GC metastasis both in vitro and in vivo. Mechanically, we demonstrated that USP1 promoted GC metastasis via upregulating ID2 expression and further confirmed that USP1 stabilized ID2 expression through deubiquitinating ID2 in GC. In conclusion, our study showed that USP1 promoted GC metastasis via stabilizing ID2 expression, which provides a potential biomarker and therapy target for GC.

scholarly journals Exosomes in Bone Sarcomas: Key Players in Metastasis

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 241 ◽  
Author(s):  
Mariona Chicón-Bosch ◽  
Oscar M. Tirado
Keyword(s):  
Tumour Progression ◽  
Survival Rates ◽  
Extracellular Vesicle ◽  
Poor Survival ◽  
Metastatic Phenotype ◽  
High Incidence ◽  
Key Players ◽  
Bone Sarcomas ◽  
Cellular Behaviour

Bone sarcomas are rare cancers which often present with metastatic disease and are still associated with poor survival rates. Studies in the last decade have identified that exosomes, a type of extracellular vesicle released by cells, play an important role in tumour progression and dissemination. Through the transfer of their cargo (RNAs, proteins, and lipids) across cells, they are involved in cellular cross-talk and can induce changes in cellular behaviour. Exosomes have been shown to be important in metastasis organotropism, induction of angiogenesis and vascular permeability, the education of cells towards a pro-metastatic phenotype or the interaction between stromal and tumour cells. Due to the importance exosomes have in disease progression and the high incidence of metastasis in bone sarcomas, recent studies have evaluated the implications of these extracellular vesicles in bone sarcomas. In this review, we discuss the studies that evaluate the role of exosomes in osteosarcoma, Ewing sarcoma, and preliminary data on chondrosarcoma.

scholarly journals Inflammation and Epithelial-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma: Fighting Against Multiple Opponents

2017 ◽  
Vol 10 ◽  
pp. 117906441770928 ◽  
Author(s):  
Farid G Khalafalla ◽  
Mohammad W Khan
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Survival Rates ◽  
Ductal Adenocarcinoma ◽  
Poor Survival ◽  
Inflammatory Signaling ◽  
Mesenchymal Transition ◽  
Enhanced Resistance ◽  
Resistance To Chemotherapy

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and one of the most lethal human cancers. Inflammation is a critical component in PDAC initiation and progression. Inflammation also contributes to the aggressiveness of PDAC indirectly via induction of epithelial-mesenchymal transition (EMT), altogether leading to enhanced resistance to chemotherapy and poor survival rates. This review gives an overview of the key pro-inflammatory signaling pathways involved in PDAC pathogenesis and discusses the role of inflammation in induction of EMT and development of chemoresistance in patients with PDAC.

792: Role of Oxidative Stress in Tumorigenic Potential of Bladder Cancer Cells

2005 ◽  
Vol 173 (4S) ◽  
pp. 214-215 ◽  
Author(s):  
Daniel Cho ◽  
Xiao Fang Ha ◽  
J. Andre Melendez ◽  
Louis J. Giorgi ◽  
Badar M. Mian
Keyword(s):  
Oxidative Stress ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Tumorigenic Potential ◽  
Bladder Cancer Cells

scholarly journals NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2999
Author(s):  
Deborah Reynaud ◽  
Roland Abi Nahed ◽  
Nicolas Lemaitre ◽  
Pierre-Adrien Bolze ◽  
Wael Traboulsi ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Cells ◽  
Major Gene ◽  
Critical Role ◽  
Orthotopic Model ◽  
Independent Manner ◽  
Maternal Immune Response ◽  
The Impact

The inflammatory gene NLRP7 is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC; (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization; and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for NLRP7, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC.

scholarly journals Overexpressed pseudogene MT1L associated with tumor immune infiltrates and indicates a worse prognosis in BLCA

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yanpeng Ding ◽  
Nuomin Liu ◽  
Mengge Chen ◽  
Yulian Xu ◽  
Sha Fang ◽  
...  
Keyword(s):  
Immune Cells ◽  
Biological Function ◽  
Prognostic Biomarker ◽  
Poor Survival ◽  
Common Cancer ◽  
Kaplan Meier ◽  
Cox Analysis ◽  
Kaplan Meier Plotter ◽  
Worse Prognosis

Abstract Background BLCA is a common cancer worldwide, and it is both aggressive and fatal. Immunotherapy (ICT) has achieved an excellent curative effect in BLCA; however, only some BLCA patients can benefit from ICT. MT1L is a pseudogene, and a previous study suggested that MT1L can be used as an indicator of prognosis in colorectal cancer. However, the role of MT1L in BLCA has not yet been determined. Methods Data were collected from TCGA, and logistic regression, Kaplan-Meier plotter, and multivariate Cox analysis were performed to demonstrate the correlation between the pseudogene MT1L and the prognosis of BLCA. To identify the association of MT1L with tumor-infiltrating immune cells, TIMER and TISIDB were utilized. Additionally, GSEA was performed to elucidate the potential biological function. Results The expression of MT1L was decreased in BLCA. Additionally, MT1L was positively correlated with immune cells, such as Tregs (ρ = 0.708) and MDSCs (ρ = 0.664). We also confirmed that MT1L is related to typical markers of immune cells, such as PD-1 and CTLA-4. In addition, a high MT1L expression level was associated with the advanced T and N and high grade in BLCA. Increased expression of MT1L was significantly associated with shorter OS times of BLCA patients (p < 0.05). Multivariate Cox analysis revealed that MT1L expression could be an independent prognostic factor in BLCA. Conclusion Collectively, our findings demonstrated that the pseudogene MT1L regulates the immune microenvironment, correlates with poor survival, and is an independent prognostic biomarker in BLCA.

scholarly journals WNT/β-catenin-suppressed FTO expression increases m6A of c-Myc mRNA to promote tumor cell glycolysis and tumorigenesis

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Xueying Yang ◽  
Fei Shao ◽  
Dong Guo ◽  
Wei Wang ◽  
Juhong Wang ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Promoter Region ◽  
Critical Role ◽  
Mrna Translation ◽  
Poor Survival ◽  
Subsequent Increase ◽  
Critical Pathways ◽  
Number Of Genes ◽  
Promote Tumor Cell

AbstractFTO removes the N6-methyladenosine (m6A) modification from genes and plays a critical role in cancer development. However, the mechanisms underlying the regulation of FTO and its subsequent impact on the regulation of the epitranscriptome remain to be further elucidated. Here, we demonstrate that FTO expression is downregulated and inversely correlated with poor survival of lung adenocarcinoma patients. Mechanistically, Wnt signaling induces the binding of EZH2 to β-catenin. This protein complex binds to the LEF/TCF-binding elements at the promoter region of FTO, where EZH2 enhances H3K27me3 and inhibits FTO expression. Downregulated FTO expression substantially enhances the m6A levels in the mRNAs of a large number of genes in critical pathways, particularly metabolic pathway genes, such as MYC. Enhanced m6A levels on MYC mRNA recruit YTHDF1 binding, which promotes MYC mRNA translation and a subsequent increase in glycolysis and proliferation of tumor cells and tumorigenesis. Our findings uncovered a critical mechanism of epitranscriptome regulation by Wnt/β-catenin-mediated FTO downregulation and underscored the role of m6A modifications of MYC mRNA in regulating tumor cell glycolysis and growth.

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