Multipolar mitosis and aneuploidy after chrysotile treatment: a consequence of abscission failure and cytokinesis regression

Autor(es)

Cortez, Beatriz Araujo ^{[1, 2]} ; Teixeira, Paula Rezende ^[2] ; Redick, Sambra ^[3] ; Doxsey, Stephen ^[3] ; Machado-Santelli, Glaucia Maria ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biociencias, Dept Genet & Biol Evolut, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Biol Celular & Desenvolvimento, Sao Paulo - Brazil

^[3] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA - USA

• Tipo de documento: Artigo Científico
• Fonte: ONCOTARGET; v. 7, n. 8, p. 8979-8992, FEB 23 2016.
• Citações Web of Science: 8

Resumo

Chrysotile, like other types of asbestos, has been associated with mesothelioma, lung cancer and asbestosis. However, the cellular abnormalities induced by these fibers involved in cancer development have not been elucidated yet. Previous works show that chrysotile fibers induce features of cancer cells, such as aneuploidy, multinucleation and multipolar mitosis. In the present study, normal and cancer derived human cell lines were treated with chrysotile and the cellular and molecular mechanisms related to generation of aneuploid cells was elucidated. The first alteration observed was cytokinesis regression, the main cause of multinucleated cells formation and centrosome amplification. The multinucleated cells formed after cytokinesis regression were able to progress through cell cycle and generated aneuploid cells after abnormal mitosis. To understand the process of cytokinesis regression, localization of cytokinetic proteins was investigated. It was observed mislocalization of Anillin, Aurora B, Septin 9 and Alix in the intercellular bridge, and no determination of secondary constriction and abscission sites. Fiber treatment also led to overexpression of genes related to cancer, cytokinesis and cell cycle. The results show that chrysotile fibers induce cellular and molecular alterations in normal and tumor cells that have been related to cancer initiation and progression, and that tetraploidization and aneuploid cell formation are striking events after fiber internalization, which could generate a favorable context to cancer development. (AU)

• Processo FAPESP: 13/07515-6 - Estudo da amplificação centrossômica e regressão da citocinese em células em cultura tratadas com crisotila
• Beneficiário: Beatriz de Araujo Cortez
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 09/17140-4 - Diferentes abordagens para o entendimento da aneuploidia: interferindo na mitose com o uso de crisotila, vincristina e encurtamento dos telômeros
• Beneficiário: Beatriz de Araujo Cortez
• Modalidade de apoio: Bolsas no Brasil - Doutorado