Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Zinc dysregulation in cancers and its potential as a therapeutic target.

ABSTRACT: Zinc is an essential element and serves as a structural or catalytic component in many proteins. Two families of transporters are involved in maintaining cellular zinc homeostasis: the ZIP (SLC39A) family that facilitates zinc influx into the cytoplasm, and the ZnT (SLC30A) family that facilitates zinc efflux from the cytoplasm. Zinc dyshomeostasis caused by the dysfunction of zinc transporters can contribute to the initiation or progression of various cancers, including prostate cancer, breast cancer, and pancreatic cancer. In addition, intracellular zinc fluctuations lead to the disturbance of certain signaling pathways involved in the malignant properties of cancer cells. This review briefly summarizes our current understanding of zinc dyshomeostasis in cancer, and discusses the potential roles of zinc or zinc transporters in cancer therapy.

SUBMITTER: Wang J

PROVIDER: S-EPMC7476080 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Zinc dysregulation in cancers and its potential as a therapeutic target.

Wang Jie J Zhao Huanhuan H Xu Zhelong Z Cheng Xinxin X

Cancer biology & medicine 20200801 3

Zinc is an essential element and serves as a structural or catalytic component in many proteins. Two families of transporters are involved in maintaining cellular zinc homeostasis: the ZIP (SLC39A) family that facilitates zinc influx into the cytoplasm, and the ZnT (SLC30A) family that facilitates zinc efflux from the cytoplasm. Zinc dyshomeostasis caused by the dysfunction of zinc transporters can contribute to the initiation or progression of various cancers, including prostate cancer, breast ...[more]

PMID: 32944394

Similar Datasets

USP10 as a Potential Therapeutic Target in Human Cancers.

Project description:Deubiquitination is a major form of post-translational protein modification involved in the regulation of protein homeostasis and various cellular processes. Deubiquitinating enzymes (DUBs), comprising about five subfamily members, are key players in deubiquitination. USP10 is a USP-family DUB featuring the classic USP domain, which performs deubiquitination. Emerging evidence has demonstrated that USP10 is a double-edged sword in human cancers. However, the precise molecular mechanisms underlying its different effects in tumorigenesis remain elusive. A possible reason is dependence on the cell context. In this review, we summarize the downstream substrates and upstream regulators of USP10 as well as its dual role as an oncogene and tumor suppressor in various human cancers. Furthermore, we summarize multiple pharmacological USP10 inhibitors, including small-molecule inhibitors, such as spautin-1, and traditional Chinese medicines. Taken together, the development of specific and efficient USP10 inhibitors based on USP10's oncogenic role and for different cancer types could be a promising therapeutic strategy.

| S-EPMC9142050 | biostudies-literature

NLRR1 Is a Potential Therapeutic Target in Neuroblastoma and MYCN-Driven Malignant Cancers.

Project description:Receptor tyrosine kinases (RTKs) receive different modulation before transmitting proliferative signals. We previously identified neuronal leucine-rich repeat 1 (NLRR1) as a positive regulator of EGF and IGF-1 signals in high-risk neuroblastoma cells. Here, we show that NLRR1 is up-regulated in various adult cancers and acts as a key regulator of tumor cell proliferation. In the extracellular domains of NLRR1, fibronectin type III (FNIII) domain is responsible for its function to promote cell proliferation. We generated monoclonal antibodies against the extracellular domains of NLRR1 (N1mAb) and screened the positive N1mAbs for growth inhibitory effect. The treatment of N1mAbs reduces tumor cell proliferation in vitro and in vivo, and sensitizes the cells to EGFR inhibitor, suggesting that NLRR1 is a novel regulatory molecule of RTK function. Importantly, epitope mapping analysis has revealed that N1mAbs with growth inhibitory effect recognize immunoglobulin-like and FNIII domains of NLRR1, which also indicates the importance of FNIII domain in the function of NLRR1. Thus, the present study provides a new insight into the development of a cancer therapy by targeting NLRR1 as a modulator of proliferative signals on cellular membrane of tumor cells.

| S-EPMC8279747 | biostudies-literature

The (pro)renin receptor: a novel biomarker and potential therapeutic target for various cancers.

Project description:BACKGROUND:The (pro) renin receptor ((P)RR) plays important roles in various pathways, such as the Wnt/?-catenin, renin-angiotensin system (RAS), MAPK/ERK and PI3K/AKT/mTOR pathways, that are involved in a wide range of physiological and pathological processes incorporating the tumorigenesis. However, our knowledge about (P) RR was mostly limited to its roles in cardiovascular and renal physiological functions and diseases. In the past 5?years, however, compelling evidence has revealed that (P) RR is aberrantly expressed in and contributes to the development of various cancers by different means. For instance, (P) RR was recently demonstrated to induce the oncogenesis of pancreatic, colorectal and brain cancers via the Wnt signaling, while promote the endometrial cancer and glioblastoma through the RAS. METHODS:Combining with the deep analysis of big data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, this review updates and summarizes the recent studies about the newly recognized roles of (P) RR in the pathophysiological processes of cancer development and its detailed functions through related pathways, as well as the novel research progress of (P) RR in related fields including the development and application of soluble (P) RR detection kit and monoclonal (P) RR antibody. RESULTS:This review provides an overview of the essential roles of (P) RR in the tumorigenesis and progression of various cancers and offers a translational outlook for the future research and clinical practices. CONCLUSION:(P) RR in the tumor tissues and/or body fluids of patients may be a novel and promising biomarker and potential therapeutic target for diagnosis, treatment and prognosis prediction in various cancers. Video Abstract.

| S-EPMC7060546 | biostudies-literature

Ceramide-Rubusoside Nanomicelles, a Potential Therapeutic Approach to Target Cancers Carrying p53 Missense Mutations.

Project description:Ceramide (Cer) is an active cellular sphingolipid that can induce apoptosis or proliferation-arrest of cancer cells. Nanoparticle-based delivery offers an effective approach for overcoming bioavailability and biopharmaceutics issues attributable to the pronounced hydrophobicity of Cer. Missense mutations of the protein p53, which have been detected in approximately 42% of cancer cases, not only lose the tumor suppression activity of wild-type p53, but also gain oncogenic functions promoting tumor progression and drug resistance. Our previous works showed that cellular Cer can eradicate cancer cells that carry a p53 deletion-mutation by modulating alternative pre-mRNA splicing, restoring wild-type p53 protein expression. Here, we report that new ceramide-rubusoside (Cer-RUB) nanomicelles considerably enhance Cer in vivo bioavailability and restore p53-dependent tumor suppression in cancer cells carrying a p53 missense mutation. Natural RUB encapsulated short-chain C6-Cer so as to form Cer-RUB nanomicelles (∼32 nm in diameter) that substantially enhanced Cer solubility and its levels in tissues and tumors of mice dosed intraperitoneally. Intriguingly, Cer-RUB nanomicelle treatments restored p53-dependent tumor suppression and sensitivity to cisplatin in OVCAR-3 ovarian cancer cells and xenograft tumors carrying p53 R248Q mutation. Moreover, Cer-RUB nanomicelles showed no signs of significant nonspecific toxicity to noncancerous cells or normal tissues, including bone marrow. Furthermore, Cer-RUB nanomicelles restored p53 phosphorylated protein and downstream function to wild-type levels in p53 R172H/+ transgenic mice. Altogether, this study, for the first time, indicates that natural Cer-RUB nanomicelles offer a feasible approach for efficaciously and safely targeting cancers carrying p53 missense mutations.

| S-EPMC7007850 | biostudies-literature

Long Noncoding RNA Small Nucleolar Host Gene: A Potential Therapeutic Target in Urological Cancers.

Project description:The incidence of urological cancer has been gradually increasing in the last few decades. However, current diagnostic tools and treatment strategies continue to have limitations. Substantial evidence shows that long noncoding RNAs (lncRNAs) play essential roles in carcinogenesis and the progression, treatment response and prognosis of multiple human cancers, including urological cancers, gastrointestinal tumours, reproductive cancers and respiratory neoplasms. LncRNA small nucleolar RNA host genes (SNHGs), a subgroup of lncRNAs, have been found to be dysregulated in tumour cell biology. In this review, we summarize the impacts of lncRNA SNHGs in urological malignancies and the underlying mechanisms.

| S-EPMC8100577 | biostudies-literature

MiR-92a Family: A Novel Diagnostic Biomarker and Potential Therapeutic Target in Human Cancers.

Project description:Purpose: This study tried to explore whether members of miR-92a family contribute to early diagnosis and prognosis for human cancers and how they work. Methods: Integrated meta-analysis retrieved from public repositories was employed to assess the clinical roles of the miR-92a family for cancer diagnosis and prognosis. Expression level of miR-92a was detected by the TCGA database and was confirmed by non-small-cell lung cancer (NSCLC) tissues. Targets of miR-92a were predicted using starbase, and validated by dual luciferase assay. Correlation between miR-92a and the target gene was assessed by linkedOmics while expression of the target gene and its role in cancer prognosis were analyzed with UALCAN and Gepia. Results: We recognized the miR-92a family could serve as a potential diagnostic biomarker with a pooled sensitivity of 0.85 [0.81-0.88] and specificity of 0.86 [0.83-0.90]. The overall hazard ratio (HR) was 2.26 [95% CI: 1.70-3.00] for high expression groups compared to low expression groups. Expression of miR-92a was identified to be upregulated in NSCLC, especially in lung squamous cell carcinoma (LUSC). Results from starbase and dual luciferase assay indicated the regulator of G-protein signaling 3 (RGS3) was a direct target of miR-92a. Statistical negative correlation was found for the expression of miR-92a and RGS3. In addition, expression of RGS3 was downregulated in NSCLC and patients with the high expression had a poor prognosis (HR = 1.3) for LUSC patients. However, results were to the contrary for lung adenocarcinoma (HR = 0.7). Conclusion: This study revealed that miR-92a family could be ideal biomarkers for cancer diagnosis and prognosis, which might function through targeting RGS3.

| S-EPMC6779690 | biostudies-literature

Stage-specific embryonic antigen-4 as a potential therapeutic target in glioblastoma multiforme and other cancers.

Project description:Glioblastoma multiforme (GBM), the grade IV astrocytoma, is the most common and aggressive brain tumor in adults. Despite advances in medical management, the survival rate of GBM patients remains poor, suggesting that identification of GBM-specific targets for therapeutic development is urgently needed. Analysis of several glycan antigens on GBM cell lines revealed that eight of 11 GBM cell lines are positive for stage-specific embryonic antigen-4 (SSEA-4), and immunohistochemical staining confirmed that 38/55 (69%) of human GBM specimens, but not normal brain tissue, were SSEA-4(+) and correlated with high-grade astrocytoma. In addition, an SSEA-4-specific mAb was found to induce complement-dependent cytotoxicity against SSEA-4(hi) GBM cell lines in vitro and suppressed GBM tumor growth in mice. Because SSEA-4 is expressed on GBM and many other types of cancers, but not on normal cells, it could be a target for development of therapeutic antibodies and vaccines.

| S-EPMC3932869 | biostudies-other

Metadherin: A Therapeutic Target in Multiple Cancers.

Project description:Altered expression of many genes and proteins is essential for cancer development and progression. Recently, the affected expression of metadherin (MTDH), also known as AEG-1 (Astrocyte Elevated Gene 1) and Lyric, has been implicated in various aspects of cancer progression and metastasis. Elevated expression of MTDH/AEG-1 has been reported in many cancers including breast, prostate, liver, and esophageal cancers, whereas its expression is low or absent in non-malignant tissues. These expression studies suggest that MTDH may represent a potential tumor associated antigen. MTDH also regulates multiple signaling pathways including PI3K/Akt, NF-?B, Wnt/?-catenin, and MAPK which cooperate to promote the tumorigenic and metastatic potential of transformed cells. Several microRNA have also been found to be associated with the increased MTDH expression in different cancers. Increased MTDH levels were linked to the tumor chemoresistance making it an attractive novel therapeutic target. In this review, we summarize data on MTDH function in various cancers.

| S-EPMC6509227 | biostudies-literature

Integrated genomic analysis of clear cell ovarian cancers identified PRKCI as a potential therapeutic target.

Project description:Clear cell ovarian cancer (CCOC) is an epithelial ovarian cancer histotype with unique pathologic, biologic and clinical features. Despite its worse prognosis than serous ovarian cancer (SOC), the genomic landscape of CCOC is less well defined. Integrated genomic analysis of CCOC allows the identification of potential therapeutic targets to improve the treatment of this tumor. Using comparative genomic hybridization and gene expression profiling, we have screened 12 CCOC cell lines and 40 tumors to identify 45 amplified and overexpressed genes. Pathways analysis of these genes identified 19 genes with cancer-related functions. Of these, PRKCI is one of the most frequently amplified and overexpressed genes and its expression induced cancer cell proliferation and migration/invasion in vitro as well as tumor growth in vivo. Targeting PRKCI by small molecule inhibitor, sodium aurothiomalate (ATM), significantly reduced the in vivo tumor growth and may be a new therapeutic strategy to improve the treatment of CCOC.

| S-EPMC5722499 | biostudies-literature

Metformin as a Therapeutic Target in Endometrial Cancers.

Project description:Endometrial cancer is the most common gynecologic malignancy in developed countries. Its increasing incidence is thought to be related in part to the rise of metabolic syndrome, which has been shown to be a risk factor for the development of hyperestrogenic and hyperinsulinemic states. This has consequently lead to an increase in other hormone-responsive cancers as well e.g., breast and ovarian cancer. The correlation between obesity, hyperglycemia, and endometrial cancer has highlighted the important role of metabolism in cancer establishment and persistence. Tumor-mediated reprogramming of the microenvironment and macroenvironment can range from induction of cytokines and growth factors to stimulation of surrounding stromal cells to produce energy-rich catabolites, fueling the growth, and survival of cancer cells. Such mechanisms raise the prospect of the metabolic microenvironment itself as a viable target for treatment of malignancies. Metformin is a biguanide drug that is a first-line treatment for type 2 diabetes that has beneficial effects on various markers of the metabolic syndrome. Many studies suggest that metformin shows potential as an adjuvant treatment for uterine and other cancers. Here, we review the evidence for metformin as a treatment for cancers of the endometrium. We discuss the available clinical data and the molecular mechanisms by which it may exert its effects, with a focus on how it may alter the tumor microenvironment. The pleiotropic effects of metformin on cellular energy production and usage as well as intercellular and hormone-based interactions make it a promising candidate for reprogramming of the cancer ecosystem. This, along with other treatments aimed at targeting tumor metabolic pathways, may lead to novel treatment strategies for endometrial cancer.

| S-EPMC6121131 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data