scholarly journals Lysosomal Calcium Channels in Autophagy and Cancer

Cancers ◽  
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.

Role of the Hsp90-Immunophilin Heterocomplex in Cancer Biology

2020 ◽  
Vol 16 (1) ◽  
pp. 19-28
Author(s):  
Sonia A. De Leo ◽  
Nadia R. Zgajnar ◽  
Gisela I. Mazaira ◽  
Alejandra G. Erlejman ◽  
Mario D. Galigniana
Keyword(s):  
Cancer Progression ◽  
Cancer Biology ◽  
Steroid Receptors ◽  
Human Cancer ◽  
Tumor Development ◽  
Biological Properties ◽  
Tetratricopeptide Repeats ◽  
Cellular Processes ◽  
Client Factors ◽  
Cancer Tissues

The identification of new factors that may function as cancer markers and become eventual pharmacologic targets is a challenge that may influence the management of tumor development and management. Recent discoveries connecting Hsp90-binding immunophilins with the regulation of signalling events that can modulate cancer progression transform this family of proteins in potential unconventional factors that may impact on the screening and diagnosis of malignant diseases. Immunophilins are molecular chaperones that group a family of intracellular receptors for immunosuppressive compounds. A subfamily of the immunophilin family is characterized by showing structural tetratricopeptide repeats, protein domains that are able to interact with the C-terminal end of the molecular chaperone Hsp90, and via the proper Hsp90-immunophilin complex, the biological properties of a number of client-proteins involved in cancer biology are modulated. Recent discoveries have demonstrated that two of the most studied members of this Hsp90- binding subfamily of immunophilins, FKBP51 and FKBP52, participate in several cellular processes such as apoptosis, carcinogenesis progression, and chemoresistance. While the expression levels of some members of the immunophilin family are affected in both cancer cell lines and human cancer tissues compared to normal samples, novel regulatory mechanisms have emerged during the last few years for several client-factors of immunophilins that are major players in cancer development and progression, among them steroid receptors, the transctiption factor NF-κB and the catalytic subunit of telomerase, hTERT. In this review, recent findings related to the biological properties of both iconic Hsp90-binding immunophilins, FKBP51 and FKBP52, are reviewed within the context of their interactions with those chaperoned client-factors. The potential roles of both immunophilins as potential cancer biomarkers and non-conventional pharmacologic targets for cancer treatment are discussed.

scholarly journals Glutathione dysregulation and the etiology and progression of human diseases

2009 ◽  
Vol 390 (3) ◽  
Author(s):  
Nazzareno Ballatori ◽  
Suzanne M. Krance ◽  
Sylvia Notenboom ◽  
Shujie Shi ◽  
Kim Tieu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Capacity ◽  
Cancer Cells ◽  
Present Report ◽  
Human Diseases ◽  
Turnover Rates ◽  
Metabolic Intermediates ◽  
Cellular Processes ◽  
Cell Functions ◽  
Proliferation And Apoptosis

Abstract Glutathione (GSH) plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis, and as a result, disturbances in GSH homeostasis are implicated in the etiology and/or progression of a number of human diseases, including cancer, diseases of aging, cystic fibrosis, and cardiovascular, inflammatory, immune, metabolic, and neurodegenerative diseases. Owing to the pleiotropic effects of GSH on cell functions, it has been quite difficult to define the role of GSH in the onset and/or the expression of human diseases, although significant progress is being made. GSH levels, turnover rates, and/or oxidation state can be compromised by inherited or acquired defects in the enzymes, transporters, signaling molecules, or transcription factors that are involved in its homeostasis, or from exposure to reactive chemicals or metabolic intermediates. GSH deficiency or a decrease in the GSH/glutathione disulfide ratio manifests itself largely through an increased susceptibility to oxidative stress, and the resulting damage is thought to be involved in diseases, such as cancer, Parkinson's disease, and Alzheimer's disease. In addition, imbalances in GSH levels affect immune system function, and are thought to play a role in the aging process. Just as low intracellular GSH levels decrease cellular antioxidant capacity, elevated GSH levels generally increase antioxidant capacity and resistance to oxidative stress, and this is observed in many cancer cells. The higher GSH levels in some tumor cells are also typically associated with higher levels of GSH-related enzymes and transporters. Although neither the mechanism nor the implications of these changes are well defined, the high GSH content makes cancer cells chemoresistant, which is a major factor that limits drug treatment. The present report highlights and integrates the growing connections between imbalances in GSH homeostasis and a multitude of human diseases.

scholarly journals Endolysosomal TRPMLs in Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 65
Author(s):  
Mengnan Xu ◽  
Xian-Ping Dong
Keyword(s):  
Cancer Progression ◽  
Antitumor Immunity ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Nutrient Sensing ◽  
Human Diseases ◽  
Cancer Development ◽  
Cellular Processes ◽  
Multiple Processes ◽  
Transient Receptor

Lysosomes, the degradative endpoints and sophisticated cellular signaling hubs, are emerging as intracellular Ca2+ stores that govern multiple cellular processes. Dys-homeostasis of lysosomal Ca2+ is intimately associated with a variety of human diseases including cancer. Recent studies have suggested that the Ca2+-permeable channels Transient Receptor Potential (TRP) Mucolipins (TRPMLs, TRPML1-3) integrate multiple processes of cell growth, division and metabolism. Dysregulation of TRPMLs activity has been implicated in cancer development. In this review, we provide a summary of the latest development of TRPMLs in cancer. The expression of TRPMLs in cancer, TRPMLs in cancer cell nutrient sensing, TRPMLs-mediated lysosomal exocytosis in cancer development, TRPMLs in TFEB-mediated gene transcription of cancer cells, TRPMLs in bacteria-related cancer development and TRPMLs-regulated antitumor immunity are discussed. We hope to guide readers toward a more in-depth discussion of the importance of lysosomal TRPMLs in cancer progression and other human diseases.

scholarly journals Regulation of Rho GTPases by RhoGDIs in Human Cancers

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1037 ◽  
Author(s):  
Cho ◽  
Kim ◽  
Baek ◽  
Kim ◽  
Lee
Keyword(s):  
Cell Migration ◽  
Cancer Progression ◽  
Anticancer Agents ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Regulatory Mechanisms ◽  
Malignant Phenotype ◽  
Cellular Processes ◽  
Human Cancers

Rho GDP dissociation inhibitors (RhoGDIs) play important roles in various cellular processes, including cell migration, adhesion, and proliferation, by regulating the functions of the Rho GTPase family. Dissociation of Rho GTPases from RhoGDIs is necessary for their spatiotemporal activation and is dynamically regulated by several mechanisms, such as phosphorylation, sumoylation, and protein interaction. The expression of RhoGDIs has changed in many human cancers and become associated with the malignant phenotype, including migration, invasion, metastasis, and resistance to anticancer agents. Here, we review how RhoGDIs control the function of Rho GTPases by regulating their spatiotemporal activity and describe the regulatory mechanisms of the dissociation of Rho GTPases from RhoGDIs. We also discuss the role of RhoGDIs in cancer progression and their potential uses for therapeutic intervention.

scholarly journals Crk and CrkL as Therapeutic Targets for Cancer Treatment

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 739
Author(s):  
Taeju Park
Keyword(s):  
Tumor Cell ◽  
Cancer Treatment ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Therapeutic Targets ◽  
Viral Oncoprotein ◽  
Mesenchymal Transition ◽  
Chemotherapy Drugs ◽  
Cell Functions

Crk and CrkL are cellular counterparts of the viral oncoprotein v-Crk. Crk and CrkL are overexpressed in many types of human cancer, correlating with poor prognosis. Furthermore, gene knockdown and knockout of Crk and CrkL in tumor cell lines suppress tumor cell functions, including cell proliferation, transformation, migration, invasion, epithelial-mesenchymal transition, resistance to chemotherapy drugs, and in vivo tumor growth and metastasis. Conversely, overexpression of tumor cells with Crk or CrkL enhances tumor cell functions. Therefore, Crk and CrkL have been proposed as therapeutic targets for cancer treatment. However, it is unclear whether Crk and CrkL make distinct or overlapping contributions to tumor cell functions in various cancer types because Crk or CrkL have been examined independently in most studies. Two recent studies using colorectal cancer and glioblastoma cells clearly demonstrated that Crk and CrkL need to be ablated individually and combined to understand distinct and overlapping roles of the two proteins in cancer. A comprehensive understanding of individual and overlapping roles of Crk and CrkL in tumor cell functions is necessary to develop effective therapeutic strategies. This review systematically discusses crucial functions of Crk and CrkL in tumor cell functions and provides new perspectives on targeting Crk and CrkL in cancer therapy.

scholarly journals The Collagen-Modifying Enzyme PLOD2 Is Induced and Required during L1-Mediated Colon Cancer Progression

2021 ◽  
Vol 22 (7) ◽  
pp. 3552
Author(s):  
Sanith Cheriyamundath ◽  
Anmol Kumar ◽  
Nancy Gavert ◽  
Thomas Brabletz ◽  
Avri Ben-Ze’ev
Keyword(s):  
Liver Metastasis ◽  
Cancer Progression ◽  
Cell Adhesion Molecule ◽  
Tumor Tissue ◽  
Normal Mucosa ◽  
Cell Compartment ◽  
Cellular Processes ◽  
Stem Cell Compartment ◽  
Colonic Crypts ◽  
Colon Cancer Progression

The overactivation of Wnt/b-catenin signaling is a hallmark of colorectal cancer (CRC) development. We identified the cell adhesion molecule L1CAM (L1) as a target of b-catenin-TCF transactivation in CRC cells. The overexpression of L1 in CRC cells confers enhanced proliferation, motility, tumorigenesis and liver metastasis, and L1 is exclusively localized in the invasive areas of human CRC tissue. A number of genes are induced after L1 transfection into CRC cells by a mechanism involving the cytoskeletal protein ezrin and the NF-kB pathway. When studying the changes in gene expression in CRC cells overexpressing L1 in which ezrin levels were suppressed by shRNA to ezrin, we discovered the collagen-modifying enzyme lysyl hydroxylase 2 (PLOD2) among these genes. We found that increased PLOD2 expression was required for the cellular processes conferred by L1, including enhanced proliferation, motility, tumorigenesis and liver metastasis, since the suppression of endogenous PLOD2 expression, or its enzymatic activity, blocked the enhanced tumorigenic properties conferred by L1. The mechanism involved in increased PLOD2 expression by L1 involves ezrin signaling and PLOD2 that affect the SMAD2/3 pathway. We found that PLOD2 is localized in the colonic crypts in the stem cell compartment of the normal mucosa and is found at increased levels in invasive areas of the tumor and, in some cases, throughout the tumor tissue. The therapeutic strategies to target PLOD2 expression might provide a useful approach for CRC treatment.

scholarly journals Role of Virally-Encoded Deubiquitinating Enzymes in Regulation of the Virus Life Cycle

2021 ◽  
Vol 22 (9) ◽  
pp. 4438
Author(s):  
Jessica Proulx ◽  
Kathleen Borgmann ◽  
In-Woo Park
Keyword(s):  
Immune Response ◽  
Life Cycle ◽  
Deubiquitinating Enzyme ◽  
Deubiquitinating Enzymes ◽  
Antiviral Immune Response ◽  
Cellular Processes ◽  
Virus Life Cycle ◽  
Infected Cells ◽  
Dependent Processes

The ubiquitin (Ub) proteasome system (UPS) plays a pivotal role in regulation of numerous cellular processes, including innate and adaptive immune responses that are essential for restriction of the virus life cycle in the infected cells. Deubiquitination by the deubiquitinating enzyme, deubiquitinase (DUB), is a reversible molecular process to remove Ub or Ub chains from the target proteins. Deubiquitination is an integral strategy within the UPS in regulating survival and proliferation of the infecting virus and the virus-invaded cells. Many viruses in the infected cells are reported to encode viral DUB, and these vial DUBs actively disrupt cellular Ub-dependent processes to suppress host antiviral immune response, enhancing virus replication and thus proliferation. This review surveys the types of DUBs encoded by different viruses and their molecular processes for how the infecting viruses take advantage of the DUB system to evade the host immune response and expedite their replication.

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

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.

scholarly journals The Role of Autophagy and lncRNAs in the Maintenance of Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1239
Author(s):  
Leila Jahangiri ◽  
Tala Ishola ◽  
Perla Pucci ◽  
Ricky M. Trigg ◽  
Joao Pereira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Regulatory Networks ◽  
Epithelial To Mesenchymal Transition ◽  
Tumour Microenvironment ◽  
Repair Capacity ◽  
Mesenchymal Transition ◽  
Cellular Processes

Cancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and the detection, characterisation, and understanding of the regulatory landscape and cellular processes that govern their maintenance may pave the way to improving prognosis, selective targeted therapy, and therapy outcomes. In this review, we have discussed the characteristics of CSCs identified in various cancer types and the role of autophagy and long noncoding RNAs (lncRNAs) in maintaining the homeostasis of CSCs. Further, we have discussed methods to detect CSCs and strategies for treatment and relapse, taking into account the requirement to inhibit CSC growth and survival within the complex backdrop of cellular processes, microenvironmental interactions, and regulatory networks associated with cancer. Finally, we critique the computationally reinforced triangle of factors inclusive of CSC properties, the process of autophagy, and lncRNA and their associated networks with respect to hypoxia, epithelial-to-mesenchymal transition (EMT), and signalling pathways.

scholarly journals LncRNA:DNA triplex-forming sites are positioned at specific areas of genome organization and are predictors for Topologically Associated Domains

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Benjamin Soibam ◽  
Ayzhamal Zhamangaraeva
Keyword(s):  
Genome Organization ◽  
Chromatin Organization ◽  
Ctcf Binding ◽  
General Mechanism ◽  
Promoter Regions ◽  
Cellular Processes ◽  
A Genome ◽  
Topologically Associated Domains ◽  
Multiple Cell ◽  
Genomic Regions

Abstract Background Chromosomes are organized into units called topologically associated domains (TADs). TADs dictate regulatory landscapes and other DNA-dependent processes. Even though various factors that contribute to the specification of TADs have been proposed, the mechanism is not fully understood. Understanding the process for specification and maintenance of these units is essential in dissecting cellular processes and disease mechanisms. Results In this study, we report a genome-wide study that considers the idea of long noncoding RNAs (lncRNAs) mediating chromatin organization using lncRNA:DNA triplex-forming sites (TFSs). By analyzing the TFSs of expressed lncRNAs in multiple cell lines, we find that they are enriched in TADs, their boundaries, and loop anchors. However, they are evenly distributed across different regions of a TAD showing no preference for any specific portions within TADs. No relationship is observed between the locations of these TFSs and CTCF binding sites. However, TFSs are located not just in promoter regions but also in intronic, intergenic, and 3’UTR regions. We also show these triplex-forming sites can be used as predictors in machine learning models to discriminate TADs from other genomic regions. Finally, we compile a list of important “TAD-lncRNAs” which are top predictors for TADs identification. Conclusions Our observations advocate the idea that lncRNA:DNA TFSs are positioned at specific areas of the genome organization and are important predictors for TADs. LncRNA:DNA triplex formation most likely is a general mechanism of action exhibited by some lncRNAs, not just for direct gene regulation but also to mediate 3D chromatin organization.

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