0
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      LATS1 Is a Mediator of Melanogenesis in Response to Oxidative Stress and Regulator of Melanoma Growth

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The LATS1 kinase has been described as a tumor suppressor in various cancers. However, its role in melanoma has not been fully elucidated. There are several processes involved in tumorigenesis, including melanin production. Melanin content positively correlates with the level of reactive oxygen species (ROS) inside the cell. Accordingly, the purpose of the study was to assess the role of LATS1 in melanogenesis and oxidative stress and its influence on tumor growth. We have knocked down LATS1 in primary melanocytes and melanoma cells and found that its expression is crucial for melanin synthesis, ROS production, and oxidative stress response. We showed that LATS1 ablation significantly decreased the melanogenesis markers’ expression and melanin synthesis in melanocyte and melanoma cell lines. Moreover, silencing LATS1 resulted in enhanced oxidative stress. Reduced melanin content in LATS1 knocked down tumors was associated with increased tumor growth, pointing to melanin’s protective role in this process. The study demonstrated that LATS1 is highly engaged in melanogenesis and oxidative stress control and affects melanoma growth. Our results may find the implications in the diagnosis and treatment of pigmentation disorders, including melanoma.

          Related collections

          Most cited references50

          • Record: found
          • Abstract: found
          • Article: not found

          Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling.

          Reactive oxygen species (ROS) are generated during mitochondrial oxidative metabolism as well as in cellular response to xenobiotics, cytokines, and bacterial invasion. Oxidative stress refers to the imbalance due to excess ROS or oxidants over the capability of the cell to mount an effective antioxidant response. Oxidative stress results in macromolecular damage and is implicated in various disease states such as atherosclerosis, diabetes, cancer, neurodegeneration, and aging. Paradoxically, accumulating evidence indicates that ROS also serve as critical signaling molecules in cell proliferation and survival. While there is a large body of research demonstrating the general effect of oxidative stress on signaling pathways, less is known about the initial and direct regulation of signaling molecules by ROS, or what we term the "oxidative interface." Cellular ROS sensing and metabolism are tightly regulated by a variety of proteins involved in the redox (reduction/oxidation) mechanism. This review focuses on the molecular mechanisms through which ROS directly interact with critical signaling molecules to initiate signaling in a broad variety of cellular processes, such as proliferation and survival (MAP kinases, PI3 kinase, PTEN, and protein tyrosine phosphatases), ROS homeostasis and antioxidant gene regulation (thioredoxin, peroxiredoxin, Ref-1, and Nrf-2), mitochondrial oxidative stress, apoptosis, and aging (p66Shc), iron homeostasis through iron-sulfur cluster proteins (IRE-IRP), and ATM-regulated DNA damage response. Copyright © 2012 Elsevier Inc. All rights reserved.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Oxidative stress: oxidants and antioxidants.

            H Sies (1997)
            An imbalance between oxidants and antioxidants in favour of the oxidants, potentially leading to damage, is termed 'oxidative stress'. Oxidants are formed as a normal product of aerobic metabolism but can be produced at elevated rates under pathophysiological conditions. Antioxidant defense involves several strategies, both enzymatic and non-enzymatic. In the lipid phase, tocopherols and carotenes as well as oxy-carotenoids are of interest, as are vitamin A and ubiquinols. In the aqueous phase, there are ascorbate, glutathione and other compounds. In addition to the cytosol, the nuclear and mitochondrial matrices and extracellular fluids are protected. Overall, these low molecular mass antioxidant molecules add significantly to the defense provided by the enzymes superoxide dismutase, catalase and glutathione peroxidases.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Mitf regulation of Dia1 controls melanoma proliferation and invasiveness.

              It is widely held that cells with metastatic properties such as invasiveness and expression of matrix metalloproteinases arise through the stepwise accumulation of genetic lesions arising from genetic instability and "clonal evolution." By contrast, we show here that in melanomas invasiveness can be regulated epigenetically by the microphthalmia-associated transcription factor, Mitf, via regulation of the DIAPH1 gene encoding the diaphanous-related formin Dia1 that promotes actin polymerization and coordinates the actin cytoskeleton and microtubule networks at the cell periphery. Low Mitf levels lead to down-regulation of Dia1, reorganization of the actin cytoskeleton, and increased ROCK-dependent invasiveness, whereas increased Mitf expression leads to decreased invasiveness. Significantly the regulation of Dia1 by Mitf also controls p27(Kip1)-degradation such that reduced Mitf levels lead to a p27(Kip1)-dependent G1 arrest. Thus Mitf, via regulation of Dia1, can both inhibit invasiveness and promote proliferation. The results imply variations in the repertoire of environmental cues that determine Mitf activity will dictate the differentiation, proliferative, and invasive/migratory potential of melanoma cells through a dynamic epigenetic mechanism.
                Bookmark

                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                18 March 2021
                March 2021
                : 22
                : 6
                : 3108
                Affiliations
                [1 ]Department of Cancer Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, Rokietnicka Street 8, 61-806 Poznan, Poland; ewelina.dondajewska@ 123456gmail.com (E.D.); mariazajaczkowska@ 123456gmail.com (M.Z.); majka.karwacka@ 123456gmail.com (M.K.); kolenda.tomek@ 123456gmail.com (T.K.); mackiewicz.aa@ 123456gmail.com (A.M.)
                [2 ]Department of Cancer Diagnostics and Immunology, Greater Poland Cancer Centre, Garbary Street 15, 61-866 Poznan, Poland
                Author notes
                Author information
                https://orcid.org/0000-0001-9078-2015
                Article
                ijms-22-03108
                10.3390/ijms22063108
                8002997
                33803640
                3b954843-6e1e-4219-93a0-4954ed3c9596
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 20 February 2021
                : 15 March 2021
                Categories
                Article

                Molecular biology
                melanoma,lats1,melanogenesis,oxidative stress
                Molecular biology
                melanoma, lats1, melanogenesis, oxidative stress

                Comments

                Comment on this article