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Frontiers in Endocrinology 2020The structurally-related peptides, gastrin and cholecystokinin (CCK), were originally discovered as humoral stimulants of gastric acid secretion and pancreatic enzyme... (Review)
Review
The structurally-related peptides, gastrin and cholecystokinin (CCK), were originally discovered as humoral stimulants of gastric acid secretion and pancreatic enzyme release, respectively. With the aid of methodological advances in biochemistry, immunochemistry, and molecular biology in the past several decades, our concept of gastrin and CCK as simple gastrointestinal hormones has changed considerably. Extensive and studies have shown that gastrin and CCK play important roles in several cellular processes including maintenance of gastric mucosa and pancreatic islet integrity, neurogenesis, and neoplastic transformation. Indeed, gastrin and CCK, as well as their receptors, are expressed in a variety of tumor cell lines, animal models, and human samples, and might contribute to certain carcinogenesis. In this review, we will briefly introduce the gastrin and CCK system and highlight the effects of gastrin and CCK in the regulation of cell proliferation and apoptosis in both normal and abnormal conditions. The potential imaging and therapeutic use of these peptides and their derivatives are also summarized.
Topics: Animals; Apoptosis; Cell Physiological Phenomena; Cell Proliferation; Cell Transformation, Neoplastic; Cholecystokinin; Gastric Mucosa; Gastrins; Humans; Pancreas; Signal Transduction
PubMed: 32210918
DOI: 10.3389/fendo.2020.00112 -
Seminars in Cancer Biology Nov 2021The complex role of NRF2 in the context of cancer continues to evolve. As a transcription factor, NRF2 regulates various genes involved in redox homeostasis, protein... (Review)
Review
The complex role of NRF2 in the context of cancer continues to evolve. As a transcription factor, NRF2 regulates various genes involved in redox homeostasis, protein degradation, DNA repair, and xenobiotic metabolism. As such, NRF2 is critical in preserving cell function and viability, particularly during stress. Importantly, NRF2 itself is regulated via a variety of mechanisms, and the mode of NRF2 activation often dictates the duration of NRF2 signaling and its role in either preventing cancer initiation or promoting cancer progression. Herein, different modes of NRF2 regulation, including oxidative stress, autophagy dysfunction, protein-protein interactions, and epigenetics, as well as pharmacological modulators targeting this cascade in cancer, are explored. Specifically, how the timing and duration of these different mechanisms of NRF2 induction affect tumor initiation, progression, and metastasis are discussed. Additionally, progress in the discovery and development of NRF2 inhibitors for the treatment of NRF2-addicted cancers is highlighted, including modulators that inhibit specific NRF2 downstream targets. Overall, a better understanding of the intricate nature of NRF2 regulation in specific cancer contexts should facilitate the generation of novel therapeutics designed to not only prevent tumor initiation, but also halt progression and ultimately improve patient wellbeing and survival.
Topics: Animals; Cell Transformation, Neoplastic; Gene Expression Regulation, Neoplastic; Humans; NF-E2-Related Factor 2; Neoplasms
PubMed: 34020028
DOI: 10.1016/j.semcancer.2021.05.016 -
Philosophical Transactions of the Royal... Mar 2014The change of a normal, healthy cell to a transformed cell is the first step in the evolutionary arc of a cancer. While the role of oncogenes in this 'passage' is well... (Review)
Review
The change of a normal, healthy cell to a transformed cell is the first step in the evolutionary arc of a cancer. While the role of oncogenes in this 'passage' is well known, the role of ion transporters in this critical step is less known and is fundamental to our understanding the early physiological processes of carcinogenesis. Cancer cells and tissues have an aberrant regulation of hydrogen ion dynamics leading to a reversal of the normal tissue intracellular to extracellular pH gradient (ΔpHi to ΔpHe). When this perturbation in pH dynamics occurs during carcinogenesis is less clear. Very early studies using the introduction of different oncogene proteins into cells observed a concordance between neoplastic transformation and a cytoplasmic alkalinization occurring concomitantly with a shift towards glycolysis in the presence of oxygen, i.e. 'Warburg metabolism'. These processes may instigate a vicious cycle that drives later progression towards fully developed cancer where the reversed pH gradient becomes ever more pronounced. This review presents our understanding of the role of pH and the NHE1 in driving transformation, in determining the first appearance of the cancer 'hallmark' characteristics and how the use of pharmacological approaches targeting pH/NHE1 may open up new avenues for efficient treatments even during the first steps of cancer development.
Topics: Cation Transport Proteins; Cell Transformation, Neoplastic; Cytoplasm; Humans; Hydrogen-Ion Concentration; Models, Biological; Oncogenes; Proton Pumps; Sodium-Hydrogen Exchanger 1; Sodium-Hydrogen Exchangers
PubMed: 24493748
DOI: 10.1098/rstb.2013.0100 -
Molecules (Basel, Switzerland) Feb 2018Melatonin is a natural indoleamine produced by the pineal gland that has many functions, including regulation of the circadian rhythm. Many studies have reported the... (Review)
Review
Melatonin is a natural indoleamine produced by the pineal gland that has many functions, including regulation of the circadian rhythm. Many studies have reported the anticancer effect of melatonin against a myriad of cancer types. Cancer hallmarks include sustained proliferation, evading growth suppressors, metastasis, replicative immortality, angiogenesis, resisting cell death, altered cellular energetics, and immune evasion. Melatonin anticancer activity is mediated by interfering with various cancer hallmarks. This review summarizes the anticancer role of melatonin in each cancer hallmark. The studies discussed in this review should serve as a solid foundation for researchers and physicians to support basic and clinical studies on melatonin as a promising anticancer agent.
Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Cell Transformation, Neoplastic; Disease Progression; Genomic Instability; Humans; Melatonin; Metabolic Networks and Pathways; Neoplasms; Neovascularization, Pathologic; Signal Transduction; Tumor Escape
PubMed: 29495398
DOI: 10.3390/molecules23030518 -
Developmental Cell Dec 2015Neoplastic transformation requires changes in cellular identity. Emerging evidence increasingly points to cellular reprogramming, a process during which fully... (Review)
Review
Neoplastic transformation requires changes in cellular identity. Emerging evidence increasingly points to cellular reprogramming, a process during which fully differentiated and functional cells lose aspects of their identity while gaining progenitor characteristics, as a critical early step during cancer initiation. This cell identity crisis persists even at the malignant stage in certain cancers, suggesting that reactivation of progenitor functions supports tumorigenicity. Here, we review recent findings that establish the essential role of cellular reprogramming during neoplastic transformation and the major players involved in it with a special emphasis on pancreatic cancer.
Topics: Animals; Cell Differentiation; Cell Lineage; Cell Transformation, Neoplastic; Cellular Reprogramming; Humans; Neoplastic Stem Cells; Pancreatic Neoplasms
PubMed: 26702828
DOI: 10.1016/j.devcel.2015.12.001 -
British Journal of Cancer Jan 2020In the last decade, the field of cancer metabolism transformed itself from being a description of the metabolic features of cancer cells to become a key component of...
In the last decade, the field of cancer metabolism transformed itself from being a description of the metabolic features of cancer cells to become a key component of cellular transformation. Now, the potential role of this field in cancer biology is ready to be unravelled.
Topics: Cell Transformation, Neoplastic; Humans; Neoplasms
PubMed: 31819199
DOI: 10.1038/s41416-019-0667-3 -
Biomedicine & Pharmacotherapy =... Jan 2021Hepatitis B X-interacting protein (HBXIP) is a conserved protein of 19 kDa that was originally identified as a binding partner of hepatitis B virus X protein. Emerging... (Review)
Review
Hepatitis B X-interacting protein (HBXIP) is a conserved protein of 19 kDa that was originally identified as a binding partner of hepatitis B virus X protein. Emerging evidence indicates that HBXIP is highly expressed in a variety of cancers and is correlated with poor clinical outcomes in cancer patients. HBXIP plays a critical role in cancer progression, but the underlying mechanisms are still unclear. In this review, we primarily focus on publications investigating HBXIP in cancer research, including its expression and clinical significance in cancer patients, its role as a coactivator of transcription factors in cancer cells, its inhibitory effects on the mitochondrial cytochrome c-caspase apoptotic pathway, as well as its roles in promoting mitosis and drug resistance in cancer cells, its regulatory effects on cancer metabolism, and its relationships with other signaling pathways or microRNAs in cancer. This review aims to compile and summarize existing knowledge of the functions of HBXIP in cancer, which provides a comprehensive reference for future studies on the oncogenic mechanisms of HBXIP.
Topics: Adaptor Proteins, Signal Transducing; Animals; Antineoplastic Agents; Cell Transformation, Neoplastic; Drug Resistance, Neoplasm; Energy Metabolism; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Oncogenes; Signal Transduction; Transcription, Genetic
PubMed: 33378953
DOI: 10.1016/j.biopha.2020.111045 -
Current Opinion in Genetics &... Feb 2020There is unequivocal evidence that telomeres are crucial for cellular homeostasis and that telomere dysfunction can elicit genome instability and potentially initiate... (Review)
Review
There is unequivocal evidence that telomeres are crucial for cellular homeostasis and that telomere dysfunction can elicit genome instability and potentially initiate events that culminate in cancer. Mounting evidence points to telomeres having a crucial role in driving local and systemic structural rearrangements that drive cancer. These include the classical 'breakage-fusion-bridge' (BFB) cycles and more recently identified genome re-shaping events like kataegis and chromothripsis. In this brief review, we outline the established and most recent advances describing the roles that telomere dysfunction has in the origin of these catastrophic genome rearrangements. We discuss how local and systemic structural rearrangements enable telomere length maintenance, by either telomerase or the alternative lengthening of telomeres, that is essential to sustain cancer cell proliferation.
Topics: Cell Proliferation; Cell Transformation, Neoplastic; Genome, Human; Genomic Instability; Humans; Neoplasms; Telomere; Telomere Homeostasis
PubMed: 32145504
DOI: 10.1016/j.gde.2020.02.005 -
Anais Da Academia Brasileira de Ciencias Dec 2007The use of chemical compounds benefits society in a number of ways. Pesticides, for instance, enable foodstuffs to be produced in sufficient quantities to satisfy the... (Review)
Review
The use of chemical compounds benefits society in a number of ways. Pesticides, for instance, enable foodstuffs to be produced in sufficient quantities to satisfy the needs of millions of people, a condition that has led to an increase in levels of life expectancy. Yet, at times, these benefits are offset by certain disadvantages, notably the toxic side effects of the chemical compounds used. Exposure to these compounds can have varying effects, ranging from instant death to a gradual process of chemical carcinogenesis. There are three stages involved in chemical carcinogenesis. These are defined as initiation, promotion and progression. Each of these stages is characterised by morphological and biochemical modifications and result from genetic and/or epigenetic alterations. These genetic modifications include: mutations in genes that control cell proliferation, cell death and DNA repair--i.e. mutations in proto-oncogenes and tumour suppressing genes. The epigenetic factors, also considered as being non-genetic in character, can also contribute to carcinogenesis via epigenetic mechanisms which silence gene expression. The control of responses to carcinogenesis through the application of several chemical, biochemical and biological techniques facilitates the identification of those basic mechanisms involved in neoplasic development. Experimental assays with laboratory animals, epidemiological studies and quick tests enable the identification of carcinogenic compounds, the dissection of many aspects of carcinogenesis, and the establishment of effective strategies to prevent the cancer which results from exposure to chemicals.
Topics: Animals; Carcinogens; Cell Transformation, Neoplastic; Humans; Neoplasms; Risk Factors
PubMed: 18066431
DOI: 10.1590/s0001-37652007000400004 -
Frontiers in Immunology 2018The intestine serves as both our largest single barrier to the external environment and the host of more immune cells than any other location in our bodies. Separating... (Review)
Review
The intestine serves as both our largest single barrier to the external environment and the host of more immune cells than any other location in our bodies. Separating these potential combatants is a single layer of dynamic epithelium composed of heterogeneous epithelial subtypes, each uniquely adapted to carry out a subset of the intestine's diverse functions. In addition to its obvious role in digestion, the intestinal epithelium is responsible for a wide array of critical tasks, including maintaining barrier integrity, preventing invasion by microbial commensals and pathogens, and modulating the intestinal immune system. Communication between these epithelial cells and resident immune cells is crucial for maintaining homeostasis and coordinating appropriate responses to disease and can occur through cell-to-cell contact or by the release or recognition of soluble mediators. The objective of this review is to highlight recent literature illuminating how cytokines and chemokines, both those made by and acting on the intestinal epithelium, orchestrate many of the diverse functions of the intestinal epithelium and its interactions with immune cells in health and disease. Areas of focus include cytokine control of intestinal epithelial proliferation, cell death, and barrier permeability. In addition, the modulation of epithelial-derived cytokines and chemokines by factors such as interactions with stromal and immune cells, pathogen and commensal exposure, and diet will be discussed.
Topics: Animals; Apoptosis; Cell Membrane Permeability; Cell Proliferation; Cell Transformation, Neoplastic; Chemokines; Cytokines; Humans; Immune System; Immunity, Mucosal; Intestinal Mucosa
PubMed: 29922293
DOI: 10.3389/fimmu.2018.01270