Head & neck · 2018
Response of head and neck epithelial cells to a DNA damage-differentiation checkpoint involving polyploidization.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Sanz-Gómez Natalia, Freije Ana, Ceballos Laura, Obeso Sergio, Sanz J Ramón, García-Reija Fe, Morales-Angulo Carmelo, Gandarillas Alberto
Аннотация
BACKGROUND: Squamous epithelia of the head and neck undergo continuous cell renewal and are continuously exposed to mutagenic hazard, the main cause of cancer. How they maintain homeostasis upon cell cycle deregulation is unclear.
METHODS: To elucidate how head and neck epithelia respond to cell cycle stress, we studied human keratinocytes from various locations (oral mucosa, tonsil, pharynx, larynx, and trachea). We made use of genotoxic or mitotic drugs (doxorubicin [DOXO], paclitaxel, and nocodazole), or chemical inhibitors of the mitotic checkpoint kinases, Aurora B and polo-like-1. We further tested the response to inactivation of p53, ectopic cyclin E, or to the chemical carcinogen 7,12-dimethylbenz[a]anthracene (DMBA).
RESULTS: All treatments provoked DNA damage or mitosis impairment and strikingly triggered squamous differentiation and polyploidization, resulting in irreversible loss of clonogenic capacity.
CONCLUSION: Keratinocytes from head and neck epithelia share a cell-autonomous squamous DNA damage-differentiation response that is common to the epidermis and might continuously protect them from cancer.
METHODS: To elucidate how head and neck epithelia respond to cell cycle stress, we studied human keratinocytes from various locations (oral mucosa, tonsil, pharynx, larynx, and trachea). We made use of genotoxic or mitotic drugs (doxorubicin [DOXO], paclitaxel, and nocodazole), or chemical inhibitors of the mitotic checkpoint kinases, Aurora B and polo-like-1. We further tested the response to inactivation of p53, ectopic cyclin E, or to the chemical carcinogen 7,12-dimethylbenz[a]anthracene (DMBA).
RESULTS: All treatments provoked DNA damage or mitosis impairment and strikingly triggered squamous differentiation and polyploidization, resulting in irreversible loss of clonogenic capacity.
CONCLUSION: Keratinocytes from head and neck epithelia share a cell-autonomous squamous DNA damage-differentiation response that is common to the epidermis and might continuously protect them from cancer.