Exosomes are small vesicles comprised of a lipid bilayer containing various proteins, RNAs and bioactive lipids. They act as intercellular messengers that give the ability to communicate between both cells of the same type and other cell types. They are released by healthy cells, both constitutively and upon cell activation and play an important role in immune system function. Exosomes are essential for healthy physiological conditions, however under pathological circumstances, they act to potentiate cellular stress and damage. This review explores the characteristics, biogenesis, role(s) in the pathogenesis of diseases and role(s) in progression of cancer of these nano-sized messages-in-a-vesicle: exosomes.
Cancer is the second leading cause of death in the United States, and about 6% of the estimated cancer diagnoses this year will be melanoma cases. Melanomas are derived from transformation of the pigment producing cells of the skin, melanocytes. Early stage melanoma is usually curable by surgical resection, but late stage or subsequent secondary metastatic tumors are treated with some success with chemotherapies, radiation and/or immunotherapies. Most cancer patients die from metastatic disease, which is especially the case in melanoma. A better understanding of tumor metastasis will provide insights and guide rational therapeutic designs. Recently, the importance of melanoma-derived exosomes in the progression of that cancer has become more apparent, namely, their role in various stages of metastasis, including the induction of migration, invasion, primary niche manipulation, immune modulation and pre-metastatic niche formation. This review focuses on the critical roles that melanoma exosomes play in the progression of this deadly disease.
Background: Eukaryotic circadian clocks require chromatin modifications and remodeling.Results: SET1 is required for proper expression of the Neurospora clock gene frequency (frq). SET1 modifies chromatin at frq with the peak in H3K4me3 occurring after the peak in activation.Conclusion: H3K4 methylation appears to mitigate White Collar complex (WCC)-mediated expression.Significance: Chromatin is a key component underlying circadian oscillations in gene expression.
The activation of G-Protein Coupled Receptors (GPCRs) by their respective ligands initiates a cascade of multiple signaling processes within the cell, regulating growth, metabolism and other essential cellular functions. Dysregulation and aberrant expression of these GPCRs and their subsequent signaling cascades are associated with many different types of pathologies, including cancer. The main life threatening complication in patients diagnosed with cancer is the dissemination of cells from the primary tumor to distant vital organs within the body, metastasis. Communication between the primary tumor, immune system, and the site of future metastasis are some of the key events in the early stages of metastasis. It has been postulated that the communication is mediated by nanovesicles that, under non-pathological conditions, are released by normal cells to relay signals to other cells in the body. These nanovesicles are called exosomes, and are utilized by the tumor cell to influence changes within the recipient cell, such as bone marrow progenitor cells, and cells within the site of future metastatic growth, in order to prepare the site for colonization. Tumor cells have been shown to release an increased number of exosomes when compared to their normal cell counterpart. Exosome production and release are regulated by proteins involved in localization, degradation and size of the multivesicular body, whose function may be altered within cancer cells, resulting in the release of an increased number of these vesicles. This review investigates the possibility of GPCR signaling cascades acting as the upstream activator of proteins involved in exosome production and release, linking a commonly targeted trans-membrane protein class with cellular communication utilized by tumor cells in early stages of metastasis.
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