Abstract
Telomerase activity is essential for human cancer cells in order to maintain telomeres and provide unlimited proliferation potential and cellular immortality. However, additional non-telomeric roles emerge for the telomerase protein TERT that can impact tumourigenesis and cancer cell properties. This review summarises our current knowledge of non-telomeric functions of telomerase in human cells, with a special emphasis on cancer cells.
Non-canonical functions of telomerase can be performed within the nucleus as well as in other cellular compartments. These telomereindependent activities of TERT influence various essential cellular processes, such as gene expression, signalling pathways, mitochondrial function as well as cell survival and stress resistance. Emerging data show the interaction of telomerase with intracellular signalling pathways such as NF-κB and WNT/β-catenin; thereby contributing to inflammation, epithelial to mesenchymal transition (EMT) and cancer invasiveness. All these different functions might contribute to tumourigenesis, and have serious consequences for cancer therapies due to increased resistance against damaging agents and prevention of cell death.
In addition, TERT has been detected in non-nuclear locations such as the cytoplasm and mitochondria. Within mitochondria TERT has been shown to decrease ROS generation, improve respiration, bind to mitochondrial DNA, increase mitochondrial membrane potential and interact with mitochondrial tRNAs. All these different non-telomere-related mechanisms might contribute towards the higher resistance of cancer cells against DNA damaging treatments and promote cellular survival. Understanding these different mechanisms and their complexity in cancer cells might help to design more effective cancer therapies in the future.
Keywords: Apoptosis, cancer, mitochondria, non-telomeric functions, shuttling, survival, telomerase.
Current Pharmaceutical Design
Title:Extra-telomeric Functions of Human Telomerase: Cancer, Mitochondria and Oxidative Stress
Volume: 20 Issue: 41
Author(s): G. Saretzki
Affiliation:
Keywords: Apoptosis, cancer, mitochondria, non-telomeric functions, shuttling, survival, telomerase.
Abstract: Telomerase activity is essential for human cancer cells in order to maintain telomeres and provide unlimited proliferation potential and cellular immortality. However, additional non-telomeric roles emerge for the telomerase protein TERT that can impact tumourigenesis and cancer cell properties. This review summarises our current knowledge of non-telomeric functions of telomerase in human cells, with a special emphasis on cancer cells.
Non-canonical functions of telomerase can be performed within the nucleus as well as in other cellular compartments. These telomereindependent activities of TERT influence various essential cellular processes, such as gene expression, signalling pathways, mitochondrial function as well as cell survival and stress resistance. Emerging data show the interaction of telomerase with intracellular signalling pathways such as NF-κB and WNT/β-catenin; thereby contributing to inflammation, epithelial to mesenchymal transition (EMT) and cancer invasiveness. All these different functions might contribute to tumourigenesis, and have serious consequences for cancer therapies due to increased resistance against damaging agents and prevention of cell death.
In addition, TERT has been detected in non-nuclear locations such as the cytoplasm and mitochondria. Within mitochondria TERT has been shown to decrease ROS generation, improve respiration, bind to mitochondrial DNA, increase mitochondrial membrane potential and interact with mitochondrial tRNAs. All these different non-telomere-related mechanisms might contribute towards the higher resistance of cancer cells against DNA damaging treatments and promote cellular survival. Understanding these different mechanisms and their complexity in cancer cells might help to design more effective cancer therapies in the future.
Export Options
About this article
Cite this article as:
Saretzki G., Extra-telomeric Functions of Human Telomerase: Cancer, Mitochondria and Oxidative Stress, Current Pharmaceutical Design 2014; 20 (41) . https://dx.doi.org/10.2174/1381612820666140630095606
DOI https://dx.doi.org/10.2174/1381612820666140630095606 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Aquaporins and Roles in Brain Health and Brain Injury
Mini-Reviews in Medicinal Chemistry SPARC in Tumor Pathophysiology and as a Potential Therapeutic Target
Current Pharmaceutical Design Exploiting Cyclooxygenase-(in)Dependent Properties of COX-2 Inhibitors for Malignant Glioma Therapy
Anti-Cancer Agents in Medicinal Chemistry Integrative Neurochemistry and Neurobiology of Social Recognition and Behavior Analyzed with Respect to CD38-Dependent Brain Oxytocin Secretion
Current Topics in Medicinal Chemistry Insulin-Like Growth Factor 2 - The Oncogene and its Accomplices
Current Pharmaceutical Design Edema-mass Ratio Based On Magnetic Resonance Imaging As A Preoperative Diagnostic Factor For Posterior Fossa Metastasis
Current Medical Imaging Epithelial-Mesenchymal Transition: Implications in Cancer Progression and Metastasis
Current Pharmaceutical Biotechnology Therapeutic Targeting of CPT-11 Induced Diarrhea: A Case for Prophylaxis
Current Drug Targets Pore-forming Peptides: A New Treatment Option for Cancer
Current Medicinal Chemistry Recent Advances in Medicinal Chemistry and Pharmaceutical Technology- Strategies for Drug Delivery to the Brain
Current Topics in Medicinal Chemistry Anti-tumor Effects of Curcuminoids in Glioblastoma Multiforme: An Updated Literature Review
Current Medicinal Chemistry The Role of Emerging Genomics and Proteomics Technologies in Cancer Drug Target Discovery
Current Cancer Drug Targets The Potential of T Cell Immunoglobulin and Mucin-Domain Containing-3 (Tim-3) in Designing Novel Immunotherapy for Bladder Cancer
Endocrine, Metabolic & Immune Disorders - Drug Targets Contextualizing the Genes Altered in Bladder Neoplasms in Pediatric and Teen Patients Allows Identifying Two Main Classes of Biological Processes Involved and New Potential Therapeutic Targets
Current Genomics Effect of Non-Ionizing Electromagnetic Fields of Anthropic Origin on Male Fertility
Current Chemical Biology Role of the Receptor Tyrosine Kinase Axl and its Targeting in Cancer Cells
Current Medicinal Chemistry Targeting the Multidrug ABCG2 Transporter with Flavonoidic Inhibitors: In Vitro Optimization and In Vivo Validation
Current Medicinal Chemistry Tropism-Modified Adenoviral and Adeno-Associated Viral Vectors for Gene Therapy
Current Gene Therapy Treatment of Anaplastic Thyroid Cancer: Is there a Role for PPARγ Agonists?
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Can PET Imaging Facilitate Optimization of Cancer Therapies?
Current Pharmaceutical Design