Head Neck. 2018 Oct 12. doi: 10.1002/hed.25376. [Epub ahead of print]
Response of head and neck epithelial cells to a DNA damage-differentiation checkpoint involving polyploidization.
Sanz-Gómez N1,
Freije A1,
Ceballos L1,
Obeso S1,2,
Sanz JR1,3,
García-Reija F1,4,
Morales-Angulo C1,2,
Gandarillas A1,5.
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.
© 2018 Wiley Periodicals, Inc.
