AI Article Synopsis
- Squamous epithelia in the head and neck experience constant cell turnover and exposure to cancer-causing agents, yet it's unclear how they maintain balance when the cell cycle is disrupted.
- Researchers investigated human keratinocytes from various sites in the head and neck using drugs that induce DNA damage and affect cell division, as well as inhibitors targeting specific kinases.
- The treatments led to DNA damage and issues with cell division, causing the cells to undergo differentiation and polyploidization, ultimately resulting in a loss of their ability to grow indefinitely, suggesting a protective mechanism against cancer.
Article Abstract
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.
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| http://dx.doi.org/10.1002/hed.25376 | DOI Listing |
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