title: Airborne particulate matter in vitro exposure induces cytoskeleton remodeling through activation of the ROCK-MYPT1-MLC pathway in A549 epithelial lung cells.
abstract: Airborne particulate matter with an aerodynamic diameter ≤10μm (PM10) is considered a risk factor for the development of lung cancer. Little is known about the cellular mechanisms by which PM10is associated with cancer, but there is evidence that its exposure can lead to an acquired invasive phenotype, apoptosis evasion, inflammasome activation, and cytoskeleton remodeling in lung epithelial cells. Cytoskeleton remodeling occurs through actin stress fiber formation, which is partially regulated through ROCK kinase activation, we aimed to investigate if this protein was activated in response to PM10exposure in A549 lung epithelial cells. Results showed that 10μg/cm2of PM10had no influence on cell viability but increased actin stress fibers, cytoplasmic ROCK expression, and phosphorylation of myosin phosphatase-targeting 1 (MYPT1) and myosin light chain (MLC) proteins, which are targeted by ROCK. The inhibition of ROCK prevented actin stress fiber formation and the phosphorylation of MYPT1 and MLC, suggesting that PM10activated the ROCK-MYPT1-MLC pathway in lung epithelial cells. The activation of ROCK1 has been involved in the acquisition of malignant phenotypes, and its induction by PM10exposure could contribute to the understanding of PM10as a risk factor for cancer development through the mechanisms associated with invasive phenotype.
authors.affiliation: Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Los Reyes Iztacala, CP 54090 Tlalnepantla, Estado de México, Mexico.
authors.forename: Yolanda I
authors.initials: YI
authors.lastname: Chirino
authors.affiliation: Instituto Nacional de Cancerología (INCan), Subdirección de Investigación Básica, San Fernando No. 22, Tlalpan, 14080 CDMX, Mexico.
authors.forename: Claudia María
authors.initials: CM
authors.lastname: García-Cuellar
authors.affiliation: Instituto Nacional de Cancerología (INCan), Subdirección de Investigación Básica, San Fernando No. 22, Tlalpan, 14080 CDMX, Mexico.
authors.forename: Carlos
authors.initials: C
authors.lastname: García-García
authors.affiliation: Unidad de Investigación Biomédica en Cáncer, INCan; Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Mexico.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Soto-Reyes
authors.affiliation: Department of Pediatrics, University of Alberta, 1048 RTF, 8308 114 St Edmonton T6G 2V2, Canada.
authors.forename: Álvaro Román
authors.initials: ÁR
authors.lastname: Osornio-Vargas
authors.affiliation: Unidad de Investigación Biomédica en Cáncer, INCan; Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Mexico.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Herrera
authors.affiliation: Unidad de Investigación Biomédica en Cáncer, INCan; Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: López-Saavedra
authors.affiliation: Instituto de Física, Universidad Nacional Autónoma de México, A.P. 20-364, 01000 CDMX, Mexico.
authors.forename: Javier
authors.initials: J
authors.lastname: Miranda
authors.affiliation: Instituto Nacional de Cancerología (INCan), Subdirección de Investigación Básica, San Fernando No. 22, Tlalpan, 14080 CDMX, Mexico.
authors.forename: Raúl
authors.initials: R
authors.lastname: Quintana-Belmares
authors.affiliation: Centro de Ciencias de la Atmósfera, Universidad Nacional Autónoma de México, 04510, CDMX, Mexico.
authors.forename: Irma Rosas
authors.initials: IR
authors.lastname: Pérez
authors.affiliation: Instituto Nacional de Cancerología (INCan), Subdirección de Investigación Básica, San Fernando No. 22, Tlalpan, 14080 CDMX, Mexico. Electronic address: syesennia@gmail.com.
authors.forename: Yesennia
authors.initials: Y
authors.lastname: Sánchez-Pérez
mesh_terms: D000072283:A549 Cells; D000393:Air Pollutants / Q000633:toxicity*; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018994:Myosin Light Chains / Q000378:metabolism*; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism*; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D015398:Signal Transduction; D022502:Stress Fibers / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D000393:Air Pollutants; D018994:Myosin Light Chains; D052638:Particulate Matter; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases; D043263:Myosin-Light-Chain Phosphatase; C490372:PPP1R12A protein, human
keywords: Actin stress fiber; Atmospheric particulate matter (PM(10)); Cytoskeleton remodeling; Invasiveness; ROCK