Inhibition of the RhoA GTPase Activity Increases Sensitivity of Melanoma Cells to UV Radiation Effects

Oxidative Medicine and Cellular Longevity
Gisele EspinhaFabio Luis Forti

Abstract

Ultraviolet radiation is the main cause of DNA damage to melanocytes and development of melanoma, one of the most lethal human cancers, which leads to metastasis due to uncontrolled cell proliferation and migration. These phenotypes are mediated by RhoA, a GTPase overexpressed or overactivated in highly aggressive metastatic tumors that plays regulatory roles in cell cycle progression and cytoskeleton remodeling. This work explores whether the effects of UV on DNA damage, motility, proliferation, and survival of human metastatic melanoma cells are mediated by the RhoA pathway. Mutant cells expressing dominant-negative (MeWo-RhoA-N19) or constitutively active RhoA (MeWo-RhoA-V14) were generated and subjected to UV radiation. A slight reduction in migration and invasion was observed in MeWo and MeWo-RhoA-V14 cells but not in MeWo-RhoA-N19 cells, which presented inefficient motility and invasiveness associated with stress fibers fragmentation. Proliferation and survival of RhoA-deficient cells were drastically reduced by UV compared to cells displaying normal or high RhoA activity, suggesting increased sensitivity to UV. Loss of RhoA activity also caused less efficient DNA repair, with elevated levels of DNA lesions such as strand...Continue Reading

References

Jul 1, 1977·Journal of the National Cancer Institute·J FoghT Orfeo
Feb 1, 1977·Journal of the National Cancer Institute·J FoghJ D Loveless
Sep 1, 1976·Proceedings of the National Academy of Sciences of the United States of America·T E CareyL J Old
Mar 1, 1988·Experimental Cell Research·N P SinghE L Schneider
Jun 29, 2000·Annual Review of Biochemistry·K KaibuchiM Amano
Jun 6, 2003·Oncogene·Chamelli JhappanGlenn Merlino
Jul 21, 2004·Archives of Dermatology·Shasa HuRobert S Kirsner
Mar 8, 2005·Mutation Research·Gerd P PfeiferAhmad Besaratinia
Jul 22, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·John J StrouseAlan S Wayne
Oct 11, 2005·Annual Review of Cell and Developmental Biology·Aron B Jaffe, Alan Hall
Dec 24, 2005·Journal of Continuing Education in Nursing·Kathy Ferguson
Apr 4, 2006·Radiation Research·Han-Chun DeFedericisHarold C Box
Jul 11, 2006·The New England Journal of Medicine·Arlo J Miller, Martin C Mihm
Sep 7, 2006·Proceedings of the National Academy of Sciences of the United States of America·Stéphane MouretThierry Douki
Nov 30, 2006·Biochemistry·Jongyun HeoSharon L Campbell
Dec 16, 2006·The Journal of Biological Chemistry·Sarah A BoswellSam W Lee
Mar 9, 2007·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·R G ZeppB Sulzberger
Jun 15, 2007·Cardiovascular Research·Kimberly W RainesSharon L Campbell
Sep 13, 2008·The Journal of Investigative Dermatology·M Raza ZaidiGlenn Merlino
Oct 11, 2008·Cell Death and Differentiation·G KroemerUNKNOWN Nomenclature Committee on Cell Death 2009
Oct 11, 2008·Expert Review of Dermatology·Brozyna AnnaSlominski Andrzej
Mar 31, 2009·Biochimica Et Biophysica Acta·R KarlssonCord Brakebusch
Apr 18, 2009·Cell Cycle·Victoria Sanz-Moreno, Christopher J Marshall
Jul 8, 2009·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Jean CadetPaolo Di Mascio
Oct 2, 2009·Carcinogenesis·William K Kaufmann
Jan 7, 2011·Journal of Nucleic Acids·Rajesh P RastogiRajeshwar P Sinha
May 27, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ahmad BesaratiniaGerd P Pfeifer
Jan 3, 2012·Current Opinion in Cell Biology·Jose Javier Bravo-CorderoJohn Condeelis
Jun 8, 2013·Journal of Cellular Biochemistry·Shinji MiwaRobert M Hoffman
Jul 11, 2013·Pigment Cell & Melanoma Research·Sandra PaveyBrian Gabrielli
Mar 12, 2015·Molecular and Cellular Biochemistry·Gisele EspinhaFabio Luis Forti
Dec 10, 2015·Oxidative Medicine and Cellular Longevity·Juliana H OsakiFabio L Forti

❮ Previous
Next ❯

Citations

Jul 14, 2017·Photodermatology, Photoimmunology & Photomedicine·Ashley Sample, Yu-Ying He
Oct 6, 2020·Frontiers in Cell and Developmental Biology·Yuli T MagalhaesFabio L Forti
Oct 20, 2020·Frontiers in Cell and Developmental Biology·Cheila BritoMarta Pojo
Feb 7, 2021·Biomolecules·Chibin ChengEnmin Li

❮ Previous
Next ❯

Datasets Mentioned

BETA
GM6001

Methods Mentioned

BETA
GTPases
GTPase
transfection
electrophoresis
flow cytometry
pull-down

Software Mentioned

ZEN
cell
Komet
Odyssey

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Autophagy & Aging: Inhibitors

The feed focuses on the role of nuclear export inhibitors and their effect on autophagy and the aging process.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.