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Over-Activation of Minichromosome Maintenance Protein 10 Promotes Genomic Instability in Early Stages of Breast Cancer.
Mughal, Muhammad Jameel; Chan, Kin Iong; Mahadevappa, Ravikiran; Wong, Sin Wa; Wai, Kit Cheng; Kwok, Hang Fai.
Afiliación
  • Mughal MJ; Cancer Centre, Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau SAR; MoE Frontiers Science Center for Precision Oncology, University of Macau, Avenida de Universidade, Taipa, Macau SAR.
  • Chan KI; Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau SAR; Department of Pathology, Kiang Wu Hospital, Macau SAR.
  • Mahadevappa R; Cancer Centre, Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau SAR; MoE Frontiers Science Center for Precision Oncology, University of Macau, Avenida de Universidade, Taipa, Macau SAR.
  • Wong SW; Cancer Centre, Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau SAR; MoE Frontiers Science Center for Precision Oncology, University of Macau, Avenida de Universidade, Taipa, Macau SAR.
  • Wai KC; Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau SAR; Department of Pathology, Kiang Wu Hospital, Macau SAR.
  • Kwok HF; Cancer Centre, Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau SAR; MoE Frontiers Science Center for Precision Oncology, University of Macau, Avenida de Universidade, Taipa, Macau SAR.
Int J Biol Sci ; 18(9): 3827-3844, 2022.
Article en En | MEDLINE | ID: mdl-35813483
Genomic instability is considered as one of the key hallmark during cancer development and progression. Cellular mechanisms, such as DNA replication initiation, DNA damage and repair response, apoptosis etc are observed to block progression of genomic instability and thereby induce protective effects against cancer. DNA replication initiation protein MCM10 has been previously observed to have an increased expression in different cancer subtypes. However, MCM10 association with genomic instability, cancer development and its relevant mechanisms remain unknown. Here, using a breast cancer model, we observe a significant association of MCM10 with the degree of clinical aggressiveness in breast cancer patients. By overexpression of MCM10, we observed that MCM10 promotes tumorigenic properties in immortal non-tumorigenic mammary cells by increasing proliferation, shortening the cell cycle, and promoting tumorigenic characters in in-vivo mimicking conditions. Furthermore, overexpression of MCM10 is found to induce accumulation of ssDNA followed by overexpression of ssDNA binding protein RPA2. Mesenchymal markers such as up-regulation of Vimentin, transcription factor Snail and Twist2, and the down-regulation of E-cadherin were observed in MCM10 overexpression cells. Overall, the findings of this study revealed a novel mechanism by which MCM10 promotes genomic instability and breast cancer progression, and effectively differentiates the active degree of breast cancer aggressiveness. Thus, MCM10 has the potential to be a clinically useful biomarker as well as a therapeutic target for future breast cancer treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Proteínas de Mantenimiento de Minicromosoma Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: Int J Biol Sci Asunto de la revista: BIOLOGIA Año: 2022 Tipo del documento: Article Pais de publicación: Australia
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Proteínas de Mantenimiento de Minicromosoma Tipo de estudio: Prognostic_studies Límite: Female / Humans Idioma: En Revista: Int J Biol Sci Asunto de la revista: BIOLOGIA Año: 2022 Tipo del documento: Article Pais de publicación: Australia