Mitochondrial Heteroplasmy Shifting as a Potential Biomarker of Cancer Progression

Cancer is a serious health problem with a high mortality rate worldwide. Given the relevance of mitochondria in numerous physiological and pathological mechanisms, such as adenosine triphosphate (ATP) synthesis, apoptosis, metabolism, cancer progression and drug resistance, mitochondrial genome (mtDNA) analysis has become of great interest in the study of human diseases, including cancer. To date, a high number of variants and mutations have been identified in different types of tumors, which coexist with normal alleles, a phenomenon named heteroplasmy. This mechanism is considered an intermediate state between the fixation or elimination of the acquired mutations. It is suggested that mutations, which confer adaptive advantages to tumor growth and invasion, are enriched in malignant cells. Notably, many recent studies have reported a heteroplasmy-shifting phenomenon as a potential shaper in tumor progression and treatment response, and we suggest that each cancer type also has a unique mitochondrial heteroplasmy-shifting profile. So far, a plethora of data evidencing correlations among heteroplasmy and cancer-related phenotypes are available, but still, not authentic demonstrations, and whether the heteroplasmy or the variation in mtDNA copy number (mtCNV) in cancer are cause or consequence remained unknown. Further studies are needed to support these findings and decipher their clinical implications and impact in the field of drug discovery aimed at treating human cancer.

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The emerging role of SPOP protein in tumorigenesis and cancer therapy

Molecular Cancer ◽

10.1186/s12943-019-1124-x ◽

2020 ◽

Vol 19 (1) ◽

Cited By ~ 6

Author(s):

Yizuo Song ◽

Yichi Xu ◽

Chunyu Pan ◽

Linzhi Yan ◽

Zhi-wei Wang ◽

...

Keyword(s):

Cancer Progression ◽

Human Cancer ◽

Critical Role ◽

Cancer Type ◽

Nuclear Speckle ◽

Ring E3 Ligase ◽

Promising Therapeutic Target ◽

Liver Cancers ◽

Ring E3

AbstractThe nuclear speckle-type pox virus and zinc finger (POZ) protein (SPOP), a representative substrate-recognition subunit of the cullin-RING E3 ligase, has been characterized to play a dual role in tumorigenesis and cancer progression. Numerous studies have determined that SPOP suppresses tumorigenesis in a variety of human malignancies such as prostate, lung, colon, gastric, and liver cancers. However, several studies revealed that SPOP exhibited oncogenic function in kidney cancer, suggesting that SPOP could exert its biological function in a cancer type-specific manner. The role of SPOP in thyroid, cervical, ovarian, bone and neurologic cancers has yet to be determined. In this review article, we describe the structure and regulation of SPOP in human cancer. Moreover, we highlight the critical role of SPOP in tumorigenesis based on three major categories: physiological evidence (animal models), pathological evidence (human cancer specimens) and biochemical evidence (downstream ubiquitin substrates). Furthermore, we note that SPOP could be a promising therapeutic target for cancer treatment.

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Fascin in Gynecological Cancers: An Update of the Literature

Cancers ◽

10.3390/cancers13225760 ◽

2021 ◽

Vol 13 (22) ◽

pp. 5760

Author(s):

Ishita Gupta ◽

Semir Vranic ◽

Hamda Al-Thawadi ◽

Ala-Eddin Al Moustafa

Keyword(s):

Cancer Progression ◽

Epstein Barr Virus ◽

Human Papillomaviruses ◽

Actin Binding ◽

Invasion And Metastasis ◽

Barr Virus ◽

Potential Biomarker ◽

Different Types ◽

Infected Cells ◽

Epstein Barr

Fascin is an actin-binding protein that is encoded by the FSCN1 gene (located on chromosome 7). It triggers membrane projections and stimulates cell motility in cancer cells. Fascin overexpression has been described in different types of human cancers in which its expression correlated with tumor growth, migration, invasion, and metastasis. Moreover, overexpression of fascin was found in oncovirus-infected cells, such as human papillomaviruses (HPVs) and Epstein-Barr virus (EBV), disrupting the cell–cell adhesion and enhancing cancer progression. Based on these findings, several studies reported fascin as a potential biomarker and a therapeutic target in various cancers. This review provides a brief overview of the FSCN1 role in various cancers with emphasis on gynecological malignancies. We also discuss fascin interactions with other genes and oncoviruses through which it might induce cancer development and progression.

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Carbazole Derivatives as Kinase-Targeting Inhibitors for Cancer Treatment

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557520666200117144701 ◽

2020 ◽

Vol 20 (6) ◽

pp. 444-465 ◽

Cited By ~ 1

Author(s):

Jessica Ceramella ◽

Domenico Iacopetta ◽

Alexia Barbarossa ◽

Anna Caruso ◽

Fedora Grande ◽

...

Keyword(s):

Cancer Progression ◽

Drug Targets ◽

Mechanisms Of Action ◽

Biological Pathways ◽

G Protein Coupled Receptors ◽

Ability To Act ◽

Different Types ◽

Activity Of Enzymes ◽

Intercalating Agents ◽

G Protein Coupled

Protein Kinases (PKs) are a heterogeneous family of enzymes that modulate several biological pathways, including cell division, cytoskeletal rearrangement, differentiation and apoptosis. In particular, due to their crucial role during human tumorigenesis and cancer progression, PKs are ideal targets for the design and development of effective and low toxic chemotherapeutics and represent the second group of drug targets after G-protein-coupled receptors. Nowadays, several compounds have been claimed to be PKs inhibitors, and some of them, such as imatinib, erlotinib and gefitinib, have already been approved for clinical use, whereas more than 30 others are in various phases of clinical trials. Among them, some natural or synthetic carbazole-based molecules represent promising PKs inhibitors due to their capability to interfere with PK activity by different mechanisms of action including the ability to act as DNA intercalating agents, interfere with the activity of enzymes involved in DNA duplication, such as topoisomerases and telomerases, and inhibit other proteins such as cyclindependent kinases or antagonize estrogen receptors. Thus, carbazoles can be considered a promising this class of compounds to be adopted in targeted therapy of different types of cancer.

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Bioinformatics Analysis Identifies CPZ as a Tumor Immunology Biomarker For Gastric Cancer

Current Bioinformatics ◽

10.2174/1574893615999200707145643 ◽

2020 ◽

Vol 15 ◽

Author(s):

Yuan Gu ◽

Ying Gao ◽

Xiaodan Tang ◽

Huizhong Xia ◽

Kunhe Shi

Keyword(s):

Gastric Cancer ◽

T Cells ◽

Signaling Pathway ◽

Tumor Immunology ◽

Bioinformatics Analysis ◽

Human Cancer ◽

Disease Free Survival ◽

Kaplan Meier ◽

Potential Biomarker ◽

Pathway Regulation

Background: Gastric cancer (GC) is one of the most common malignancies worldwide. However, the biomarkers for the prognosis and diagnosis of Gastric cancer were still need. Objective: The present study aimed to evaluate whether CPZ could be a potential biomarker for GC. Method: Kaplan-Meier plotter (http://kmplot.com/analysis/) was used to determine the correlation between CPZ expression and overall survival (OS) and disease-free survival (DFS) time in GC [9]. We analyzed CPZ expression in different types of cancer and the correlation of CPZ expression with the abundance of immune infiltrates, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells, via gene modules using TIMER Database. Results: The present study identified that CPZ was overexpressed in multiple types of human cancer, including Gastric cancer. We found that overexpression of CPZ correlates to the poor prognosis of patients with STAD. Furthermore, our analyses show that immune infiltration levels and diverse immune marker sets are correlated with levels of CPZ expression in STAD. Bioinformatics analysis revealed that CPZ was involved in regulating multiple pathways, including PI3K-Akt signaling pathway, cGMP-PKG signaling pathway, Rap1 signaling pathway, TGF-beta signaling pathway, regulation of cell adhesion, extracellular matrix organization, collagen fibril organization, collagen catabolic process. Conclusion: This study for the first time provides useful information to understand the potential roles of CPZ in tumor immunology and validate it to be a potential biomarker for GC.

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Circulating Cell-Free DNA in Liquid Biopsies as Potential Biomarker for Bladder Cancer: A Review

Cancers ◽

10.3390/cancers13061448 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1448

Author(s):

Raquel Herranz ◽

Julia Oto ◽

Emma Plana ◽

Álvaro Fernández-Pardo ◽

Fernando Cana ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Progression ◽

Specific Treatment ◽

Predictive Biomarkers ◽

Liquid Biopsies ◽

Cell Free Dna ◽

Specific Patient ◽

Free Dna ◽

Potential Biomarker ◽

Cancer Types

Bladder cancer (BC) is among the most frequent cancer types in the world and is the most lethal urological malignancy. Presently, diagnostic and follow-up methods for BC are expensive and invasive. Thus, the identification of novel predictive biomarkers for diagnosis, progression, and prognosis of BC is of paramount importance. To date, several studies have evidenced that cell-free DNA (cfDNA) found in liquid biopsies such as blood and urine may play a role in the particular scenario of urologic tumors, and its analysis may improve BC diagnosis report about cancer progression or even evaluate the effectiveness of a specific treatment or anticipate whether a treatment would be useful for a specific patient depending on the tumor characteristics. In the present review, we have summarized the up-to-date studies evaluating the value of cfDNA as potential diagnostic, prognostic, or monitoring biomarker for BC in several biofluids.

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Transporter associated with antigen processing 1 (TAP1) expression and prognostic analysis in breast, lung, liver, and ovarian cancer

Journal of Molecular Medicine ◽

10.1007/s00109-021-02088-w ◽

2021 ◽

Author(s):

Anika Tabassum ◽

Md. Nazmus Samdani ◽

Tarak Chandra Dhali ◽

Rahat Alam ◽

Foysal Ahammad ◽

...

Keyword(s):

Expression Pattern ◽

Cancer Progression ◽

Antigen Processing ◽

Human Cancer ◽

Analytical Data ◽

Significant Negative Correlation ◽

Cancer Tissue ◽

Human Cancer Cell Lines ◽

Prognostic Analysis ◽

Cancer Types

Abstract Transporter associated with antigen processing 1 (TAP1) is a transporter protein that represent tumor antigen in the MHC I or HLA complex. Any defect in the TAP1 gene resulting in inadequate tumor tracking. TAP1 influences multidrug resistance (MDR) in human cancer cell lines and hinders the treatment during chemotherapeutic. The association of TAP1 in cancer progression remains mostly unknown and further study of the gene in relation with cancer need to conduct. Thus, the study has designed to analyze the association between the TAP1 with cancer by computationally. The expression pattern of the gene has determined by using ONCOMINE, GENT2, and GEPIA2 online platforms. The protein level of TAP1 was examined by the help of Human Protein Atlas. Samples with different clinical outcomes were investigated to evaluate the expression and promoter methylation in cancer vs. normal tissues by using UALCAN server. The copy number alteration, mutation frequency, and expression level of the gene in different cancer were analyzed by using cBioPortal server. The PrognoScan and KM plotter platforms were used to perform the survival analysis and represented graphically. Additionally, pathway and gene ontology (GO) features correlated to the TAP1 gene were analyzed and presented by bar charts. After arranging the data in a single panel like correlating expression to prognosis, mutational and alterations characteristic, and pathways analysis, we observed some interesting insights that emphasized the importance of the gene in cancer progression. The study found the relationship between the TAP1 expression pattern and prognosis in different cancer tissues and shows how TAP1 affects the clinical characteristics. The analytical data presented in the study is vital to learn about the effect of TAP1 in tumor tissue, where previously studies showing contradicting expression of TAP1 in cancer tissue. The analyzed data can also be utilized further to evade the threats against chemotherapy. Overall, the study provided a new aspect to consider the role of TAP1 gene in cancer progression and survival status. Key messages • This study demonstrated, for the first time, a correlation between the TAP1 gene and tumor progression. • An upregulation of TAP1 mRNA was demonstrated in various cancer types. • This study reported a significant negative correlation for TAP1 gene expression and the survival rate in different cancer types.

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Detection of Prostate Cancer via IR Spectroscopic Analysis of Urinary Extracellular Vesicles: A Pilot Study

Membranes ◽

10.3390/membranes11080591 ◽

2021 ◽

Vol 11 (8) ◽

pp. 591

Author(s):

Xin-Le Yap ◽

Bayden Wood ◽

Teng-Aik Ong ◽

Jasmine Lim ◽

Bey-Hing Goh ◽

...

Keyword(s):

Prostate Cancer ◽

Extracellular Vesicles ◽

Cancer Progression ◽

Prostate Cancer Screening ◽

Principal Component ◽

Urine Samples ◽

Cancer Type ◽

Marker Proteins ◽

Novel Strategy ◽

Ir Spectroscopic

Extracellular vesicles (EVs) are membranous nanoparticles naturally released from living cells which can be found in all types of body fluids. Recent studies found that cancer cells secreted EVs containing the unique set of biomolecules, which give rise to a distinctive absorbance spectrum representing its cancer type. In this study, we aimed to detect the medium EVs (200–300 nm) from the urine of prostate cancer patients using Fourier transform infrared (FTIR) spectroscopy and determine their association with cancer progression. EVs extracted from 53 urine samples from patients suspected of prostate cancer were analyzed and their FTIR spectra were preprocessed for analysis. Characterization of morphology, particle size and marker proteins confirmed that EVs were successfully isolated from urine samples. Principal component analysis (PCA) of the EV’s spectra showed the model could discriminate prostate cancer with a sensitivity of 59% and a specificity of 81%. The area under curve (AUC) of FTIR PCA model for prostate cancer detection in the cases with 4–20 ng/mL PSA was 0.7, while the AUC for PSA alone was 0.437, suggesting the analysis of urinary EVs described in this study may offer a novel strategy for the development of a noninvasive additional test for prostate cancer screening.

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Lysyl Oxidase Mechanisms to Mediate Gastrointestinal Cancer Progression

Gastrointestinal Tumors ◽

10.1159/000511244 ◽

2020 ◽

pp. 1-10

Author(s):

Ahmadshah Farhat ◽

Gordon A. Ferns ◽

Korosh Ashrafi ◽

Mohammad-Hassan Arjmand

Keyword(s):

Cancer Progression ◽

Extracellular Enzymes ◽

Lysyl Oxidase ◽

Ecm Remodeling ◽

Complex Process ◽

High Prevalence ◽

Different Types ◽

Fibrotic Diseases ◽

Gi Cancers ◽

Improvement In Survival

Background: Malignancy is a complex process resulting from different changes such as extracellular matrix (ECM) remodeling and stiffness. One of the important enzymes that contribute to ECM remodeling is lysyl oxidase (Lox) that is overexpressed in different types of human cancers. Because of the high prevalence and poor survival of gastrointestinal (GI) malignancies in this review, we discuss the association between Lox activity and the progression of GI cancers. Lox proteins are a group of extracellular enzymes that catalyzed the cross-linking of collagen and elastin, so they have important roles in the control of structure and homeostasis of ECM. Abnormal activation and expression of the Lox family of proteins lead to changes in the ECM toward increased rigidity and fibrosis. Stiffness of ECM can contribute to the pathogenesis of cancers. Summary: Dysregulation of Lox expression is a factor in both fibrotic diseases and cancer. ECM stiffness by Lox overactivity creates a physical barrier against intratumoral concentration of chemotherapeutic drugs and facilitates cancer inflammation, angiogenesis, and metastasis. Key Message: Because of the roles of Lox in GI cancers, development targeting Lox protein isotypes may be an appropriate strategy for treatment of GI cancers and improvement in survival of patients.

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Genome-wide methylation sequencing identifies progression-related epigenetic drivers in myelodysplastic syndromes

Cell Death and Disease ◽

10.1038/s41419-020-03213-2 ◽

2020 ◽

Vol 11 (11) ◽

Author(s):

Jing-dong Zhou ◽

Ting-juan Zhang ◽

Zi-jun Xu ◽

Zhao-qun Deng ◽

Yu Gu ◽

...

Keyword(s):

Cancer Progression ◽

Myelodysplastic Syndromes ◽

Bisulfite Sequencing ◽

De Novo ◽

Dna Hypermethylation ◽

Reduced Representation ◽

Targeted Bisulfite Sequencing ◽

Specific Pcr ◽

Genome Wide ◽

Potential Biomarker

AbstractThe potential mechanism of myelodysplastic syndromes (MDS) progressing to acute myeloid leukemia (AML) remains poorly elucidated. It has been proved that epigenetic alterations play crucial roles in the pathogenesis of cancer progression including MDS. However, fewer studies explored the whole-genome methylation alterations during MDS progression. Reduced representation bisulfite sequencing was conducted in four paired MDS/secondary AML (MDS/sAML) patients and intended to explore the underlying methylation-associated epigenetic drivers in MDS progression. In four paired MDS/sAML patients, cases at sAML stage exhibited significantly increased methylation level as compared with the matched MDS stage. A total of 1090 differentially methylated fragments (DMFs) (441 hypermethylated and 649 hypomethylated) were identified involving in MDS pathogenesis, whereas 103 DMFs (96 hypermethylated and 7 hypomethylated) were involved in MDS progression. Targeted bisulfite sequencing further identified that aberrant GFRA1, IRX1, NPY, and ZNF300 methylation were frequent events in an additional group of de novo MDS and AML patients, of which only ZNF300 methylation was associated with ZNF300 expression. Subsequently, ZNF300 hypermethylation in larger cohorts of de novo MDS and AML patients was confirmed by real-time quantitative methylation-specific PCR. It was illustrated that ZNF300 methylation could act as a potential biomarker for the diagnosis and prognosis in MDS and AML patients. Functional experiments demonstrated the anti-proliferative and pro-apoptotic role of ZNF300 overexpression in MDS-derived AML cell-line SKM-1. Collectively, genome-wide DNA hypermethylation were frequent events during MDS progression. Among these changes, ZNF300 methylation, a regulator of ZNF300 expression, acted as an epigenetic driver in MDS progression. These findings provided a theoretical basis for the usage of demethylation drugs in MDS patients against disease progression.

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Lysosomal Calcium Channels in Autophagy and Cancer

Cancers ◽

10.3390/cancers13061299 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1299

Author(s):

Yi Wu ◽

Peng Huang ◽

Xian-Ping Dong

Keyword(s):

Calcium Channels ◽

Cancer Progression ◽

Human Cancer ◽

Human Diseases ◽

Cellular Processes ◽

Cell Functions ◽

Multiple Cell ◽

Dependent Processes ◽

Intracellular Messenger

Ca2+ is pivotal intracellular messenger that coordinates multiple cell functions such as fertilization, growth, differentiation, and viability. Intracellular Ca2+ signaling is regulated by both extracellular Ca2+ entry and Ca2+ release from intracellular stores. Apart from working as the cellular recycling center, the lysosome has been increasingly recognized as a significant intracellular Ca2+ store that provides Ca2+ to regulate many cellular processes. The lysosome also talks to other organelles by releasing and taking up Ca2+. In lysosomal Ca2+-dependent processes, autophagy is particularly important, because it has been implicated in many human diseases including cancer. This review will discuss the major components of lysosomal Ca2+ stores and their roles in autophagy and human cancer progression.

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