Targeting Never-In-Mitosis-A Related Kinase 5 in Cancer: A Review

2021 ◽  
Vol 28 ◽  
Author(s):  
Margarite D. Matossian ◽  
Carrow I. Wells ◽  
William J. Zuercher ◽  
Bridgette M. Collins-Burow ◽  
David H. Drewry ◽  
...  
Keyword(s):  
Cancer Biology ◽  
Current Knowledge ◽  
Tumor Development ◽  
Mitotic Kinases ◽  
Cellular Processes ◽  
Physiologic Function ◽  
Therapeutic Development ◽  
Cell Processes ◽  
Tumor Types ◽  
Pharmacologic Inhibition

: Mitotic kinases have integral roles in cell processes responsible for cancer development and progression in all tumor types and are common targets for therapeutics. However, a large subset of the human kinome remains unexplored with respect to functionality in cancer systems. Within the mitotic kinases, the never-in-mitosis kinase (NEK) family, are emerging as novel kinase targets in various cancer types. NEK5 is an understudied member of the NEK family. While there are more recent studies describing physiologic function of NEK5, its role in cancer biology remains widely understudied. However, emerging studies implicate NEK5 has potentially crucial functions in various solid tumors. In this review we discuss current knowledge regarding a role for NEK5 in cancer, and implications of NEK5 expression and activity in tumor development and metastasis. We summarize current studies that examine NEK5 activity in diverse cancer systems and cellular processes. As an understudied kinase, there are currently no selective NEK5-targeting agents to test effects of pharmacologic inhibition in cancer, although there exist recent advancements in this area. Here we also include an update on efforts to develop selective pharmacologic inhibition of NEK5 and we discuss the current direction of NEK5-targeting therapeutic development. Generation of selective NEK5 inhibitors are promising new targeted therapies for cancer growth and metastasis.

scholarly journals MicroRNA in Ovarian Cancer: Biology, Pathogenesis, and Therapeutic Opportunities

2019 ◽  
Vol 16 (9) ◽  
pp. 1510 ◽  
Author(s):  
San-Nung Chen ◽  
Renin Chang ◽  
Li-Te Lin ◽  
Chyi-Uei Chern ◽  
Hsiao-Wen Tsai ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Messenger Rna ◽  
Cancer Biology ◽  
Cancer Metastasis ◽  
Female Reproductive System ◽  
Future Perspectives ◽  
Action Current ◽  
Cellular Processes ◽  
New Biomarkers ◽  
Tumor Types

Ovarian cancer comprises one of the three major malignant tumor types in the female reproductive system. The mortality rate of this cancer is the highest among all gynecological tumors, with ovarian cancer metastasis constituting an important cause of death. Therefore, markers for disease prediction and prognosis are highly desirable for early diagnosis as well as for helping optimize and personalize treatment. Recently, microRNAs (miRNAs), which consist of short-sequence RNAs that do not encode a protein, have emerged as new biomarkers in the clinical diagnosis and treatment of ovarian cancer. By pairing with bases specific to the target messenger RNA (mRNA), miRNAs cause degradation of the target mRNA or inhibit its translation, thereby regulating various cellular processes including cell proliferation and adhesion. Increasing numbers of studies have shown that miRNA expression abnormality plays an important role in the development of ovarian cancer. In this review, we discuss the mechanisms of miRNA action, current research regarding their role in the suppression or promotion of ovarian cancer, and their use as markers for diagnosis of prognosis or as therapeutic targets for this disease. Finally, we present future perspectives regarding the clinical management of ovarian cancer and the role for miRNAs therein.

Malignant Nonhematological Effusion Characterization by Flow Cytometry

2016 ◽  
Vol 60 (4) ◽  
pp. 365-371 ◽  
Author(s):  
Ben Davidson
Keyword(s):  
Flow Cytometry ◽  
Cancer Biology ◽  
Current Knowledge ◽  
Quantitative Detection ◽  
Routine Practice ◽  
Stem Cell Markers ◽  
Cellular Processes ◽  
Proliferation And Apoptosis ◽  
Malignant Effusions ◽  
Monitoring Treatment

With the exception of hematological malignancies, flow cytometry (FC) is infrequently applied as an ancillary tool in the diagnosis of malignant effusions in most institutions. However, FC may be effectively used to differentiate between epithelial cells, mesothelial cells and leukocytes using antibodies against both cell surface and intracellular proteins, offering the advantage of quantitative analysis. Additionally, FC may be applied to the quantitative detection of cancer-associated molecules, including stem cell markers, as well as assessment of critical cellular processes, such as proliferation and apoptosis. Some of the latter tests may have relevance for monitoring treatment response in the presence of metastatic disease, although this does not constitute routine practice to date. This review summarizes current knowledge regarding the application of FC to serous effusions in the diagnostic setting, as well as in research into cancer biology focusing on clinical specimens. The studies published to date suggest a role for this method in the clinical setting in the context of diagnosis, prediction and prognosis.

scholarly journals Y RNA: An Overview of Their Role as Potential Biomarkers and Molecular Targets in Human Cancers

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1238 ◽  
Author(s):  
Caterina Gulìa ◽  
Fabrizio Signore ◽  
Marco Gaffi ◽  
Silvia Gigli ◽  
Raffaella Votino ◽  
...  
Keyword(s):  
Cancer Biology ◽  
Current Knowledge ◽  
Non Invasive ◽  
Bodily Fluids ◽  
Oncological Patients ◽  
Non Coding Rna ◽  
Tumor Types ◽  
Established Role ◽  
Inhibit Cell Proliferation

Y RNA are a class of small non-coding RNA that are largely conserved. Although their discovery was almost 40 years ago, their function is still under investigation. This is evident in cancer biology, where their role was first studied just a dozen years ago. Since then, only a few contributions were published, mostly scattered across different tumor types and, in some cases, also suffering from methodological limitations. Nonetheless, these sparse data may be used to make some estimations and suggest routes to better understand the role of Y RNA in cancer formation and characterization. Here we summarize the current knowledge about Y RNA in multiple types of cancer, also including a paragraph about tumors that might be included in this list in the future, if more evidence becomes available. The picture arising indicates that Y RNA might be useful in tumor characterization, also relying on non-invasive methods, such as the analysis of the content of extracellular vesicles (EV) that are retrieved from blood plasma and other bodily fluids. Due to the established role of Y RNA in DNA replication, it is possible to hypothesize their therapeutic targeting to inhibit cell proliferation in oncological patients.

Exploiting S-nitrosylation for cancer therapy: facts and perspectives

2020 ◽  
Vol 477 (19) ◽  
pp. 3649-3672
Author(s):  
Salvatore Rizza ◽  
Giuseppe Filomeni
Keyword(s):  
Nitric Oxide ◽  
Cancer Biology ◽  
Synthetic Lethality ◽  
Current Knowledge ◽  
Tissue Homeostasis ◽  
Loss Of Function ◽  
Post Translational Modification ◽  
Cellular Processes ◽  
Insight Into

S-nitrosylation, the post-translational modification of cysteines by nitric oxide, has been implicated in several cellular processes and tissue homeostasis. As a result, alterations in the mechanisms controlling the levels of S-nitrosylated proteins have been found in pathological states. In the last few years, a role in cancer has been proposed, supported by the evidence that various oncoproteins undergo gain- or loss-of-function modifications upon S-nitrosylation. Here, we aim at providing insight into the current knowledge about the role of S-nitrosylation in different aspects of cancer biology and report the main anticancer strategies based on: (i) reducing S-nitrosylation-mediated oncogenic effects, (ii) boosting S-nitrosylation to stimulate cell death, (iii) exploiting S-nitrosylation through synthetic lethality.

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.

Long noncoding RNAs: lincs between human health and disease

2017 ◽  
Vol 45 (3) ◽  
pp. 805-812 ◽  
Author(s):  
Zhi Hao Kwok ◽  
Yvonne Tay
Keyword(s):  
Cancer Biology ◽  
High Throughput Sequencing ◽  
Current Knowledge ◽  
Noncoding Rnas ◽  
Clinical Applications ◽  
Long Noncoding Rnas ◽  
Cellular Processes ◽  
Health And Disease ◽  
Underlying Mechanisms ◽  
Sequencing Platforms

Long noncoding RNAs (lncRNAs) represent one of the largest classes of transcripts and are highly diverse in terms of characteristics and functions. Advances in high-throughput sequencing platforms have enabled the rapid discovery and identification of lncRNAs as key regulatory molecules involved in various cellular processes and their dysregulation in various human diseases. Here, we summarize the current knowledge of the functions and underlying mechanisms of lncRNA activity with a particular focus on cancer biology. We also discuss the potential of lncRNAs as diagnostic and therapeutic targets for clinical applications.

scholarly journals Skeletal Muscle Deconditioning in Breast Cancer Patients Undergoing Chemotherapy: Current Knowledge and Insights From Other Cancers

2021 ◽  
Vol 9 ◽  
Author(s):  
Joris Mallard ◽  
Elyse Hucteau ◽  
Thomas J. Hureau ◽  
Allan F. Pagano
Keyword(s):  
Breast Cancer ◽  
Skeletal Muscle ◽  
Cancer Patients ◽  
Current Knowledge ◽  
Tumor Development ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Cellular Mechanisms ◽  
Cross Sectional ◽  
Cellular Processes

Breast cancer represents the most commonly diagnosed cancer while neoadjuvant and adjuvant chemotherapies are extensively used in order to reduce tumor development and improve disease-free survival. However, chemotherapy also leads to severe off-target side-effects resulting, together with the tumor itself, in major skeletal muscle deconditioning. This review first focuses on recent advances in both macroscopic changes and cellular mechanisms implicated in skeletal muscle deconditioning of breast cancer patients, particularly as a consequence of the chemotherapy treatment. To date, only six clinical studies used muscle biopsies in breast cancer patients and highlighted several important aspects of muscle deconditioning such as a decrease in muscle fibers cross-sectional area, a dysregulation of protein turnover balance and mitochondrial alterations. However, in comparison with the knowledge accumulated through decades of intensive research with many different animal and human models of muscle atrophy, more studies are necessary to obtain a comprehensive understanding of the cellular processes implicated in breast cancer-mediated muscle deconditioning. This understanding is indeed essential to ultimately lead to the implementation of efficient preventive strategies such as exercise, nutrition or pharmacological treatments. We therefore also discuss potential mechanisms implicated in muscle deconditioning by drawing a parallel with other cancer cachexia models of muscle wasting, both at the pre-clinical and clinical levels.

scholarly journals MiR-7 in Cancer Development

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 325
Author(s):  
Petra Korać ◽  
Mariastefania Antica ◽  
Maja Matulić
Keyword(s):  
Cell Fate ◽  
Dominant Role ◽  
Tumor Development ◽  
Mrna Translation ◽  
Cell Types ◽  
Fine Tuning ◽  
Non Coding Rna ◽  
Tumor Types ◽  
Different Cell Types ◽  
The Brain

MicroRNAs (miRNAs) are short non-coding RNA involved in the regulation of specific mRNA translation. They participate in cellular signaling circuits and can act as oncogenes in tumor development, so-called oncomirs, as well as tumor suppressors. miR-7 is an ancient miRNA involved in the fine-tuning of several signaling pathways, acting mainly as tumor suppressor. Through downregulation of PI3K and MAPK pathways, its dominant role is the suppression of proliferation and survival, stimulation of apoptosis and inhibition of migration. Besides these functions, it has numerous additional roles in the differentiation process of different cell types, protection from stress and chromatin remodulation. One of the most investigated tissues is the brain, where its downregulation is linked with glioblastoma cell proliferation. Its deregulation is found also in other tumor types, such as in liver, lung and pancreas. In some types of lung and oral carcinoma, it can act as oncomir. miR-7 roles in cell fate determination and maintenance of cell homeostasis are still to be discovered, as well as the possibilities of its use as a specific biotherapeutic.

scholarly journals Advances in the Regulation of Mammalian Follicle-Stimulating Hormone Secretion

Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 1134
Author(s):  
Hao-Qi Wang ◽  
Wei-Di Zhang ◽  
Bao Yuan ◽  
Jia-Bao Zhang
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Follicle Stimulating Hormone ◽  
Hormone Secretion ◽  
Β Subunit ◽  
Glycoprotein Hormone ◽  
Livestock Breeding ◽  
Biological Specificity ◽  
Therapeutic Development ◽  
Stimulating Hormone

Mammalian reproduction is mainly driven and regulated by the hypothalamic-pituitary-gonadal (HPG) axis. Follicle-stimulating hormone (FSH), which is synthesized and secreted by the anterior pituitary gland, is a key regulator that ultimately affects animal fertility. As a dimeric glycoprotein hormone, the biological specificity of FSH is mainly determined by the β subunit. As research techniques are being continuously innovated, studies are exploring the underlying molecular mechanism regulating the secretion of mammalian FSH. This article will review the current knowledge on the molecular mechanisms and signaling pathways systematically regulating FSH synthesis and will present the latest hypothesis about the nuclear cross-talk among the various endocrine-induced pathways for transcriptional regulation of the FSH β subunit. This article will provide novel ideas and potential targets for the improved use of FSH in livestock breeding and therapeutic development.

scholarly journals The Role of Preclinical Models in Creatine Transporter Deficiency: Neurobiological Mechanisms, Biomarkers and Therapeutic Development

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1123
Author(s):  
Elsa Ghirardini ◽  
Francesco Calugi ◽  
Giulia Sagona ◽  
Federica Di Vetta ◽  
Martina Palma ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Human Condition ◽  
Clinical Aspects ◽  
Missense Mutations ◽  
Preclinical Development ◽  
Creatine Transporter Deficiency ◽  
Therapeutic Development ◽  
Transporter Deficiency ◽  
Scientific Challenge ◽  
Slc6a8 Gene

Creatine (Cr) Transporter Deficiency (CTD) is an X-linked metabolic disorder, mostly caused by missense mutations in the SLC6A8 gene and presenting with intellectual disability, autistic behavior, and epilepsy. There is no effective treatment for CTD and patients need lifelong assistance. Thus, the research of novel intervention strategies is a major scientific challenge. Animal models are an excellent tool to dissect the disease pathogenetic mechanisms and drive the preclinical development of therapeutics. This review illustrates the current knowledge about Cr metabolism and CTD clinical aspects, with a focus on mainstay diagnostic and therapeutic options. Then, we discuss the rodent models of CTD characterized in the last decade, comparing the phenotypes expressed within clinically relevant domains and the timeline of symptom development. This analysis highlights that animals with the ubiquitous deletion/mutation of SLC6A8 genes well recapitulate the early onset and the complex pathological phenotype of the human condition. Thus, they should represent the preferred model for preclinical efficacy studies. On the other hand, brain- and cell-specific conditional mutants are ideal for understanding the basis of CTD at a cellular and molecular level. Finally, we explain how CTD models might provide novel insight about the pathogenesis of other disorders, including cancer.

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