Title :

Pre-malignant transformation by senescence evasion is prevented by the perk and atf6alpha branches of the unfolded protein response

Author(s) :

Drullion, Claire [Auteur]
Marot, Guillemette [Auteur]
Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694
Martin, Nathalie [Auteur]
Desle, Julie [Auteur]
Saas, Laure [Auteur]
Salazar-Cardozo, Clara [Auteur]
Bouali, Fatima [Auteur]
Mécanismes de la Tumorigénèse et Thérapies Ciblées (M3T) - UMR 8161
Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 [M3T]
Pourtier, Albin [Auteur]
Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 [M3T]
Mécanismes de la Tumorigénèse et Thérapies Ciblées (M3T) - UMR 8161
Abbadie, Corinne [Auteur]
Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 [M3T]
Mécanismes de la Tumorigénèse et Thérapies Ciblées (M3T) - UMR 8161
Pluquet, Olivier [Auteur]
Mécanismes de la Tumorigénèse et Thérapies Ciblées (M3T) - UMR 8161
Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 [M3T]

Journal title :

Cancer letters

Abbreviated title :

Cancer Lett.

Publication date :

2018-09-11

ISSN :

1872-7980

English keyword(s) :

Unfolded protein response
Normal human epidermal keratinocyte
Post-senescence neoplastic emergence
Senescence
Endoplasmic reticulum
ATF6 alpha
PERK

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

The incidence of carcinomas highly increases with age. However, the initial steps of the age-related molecular carcinogenic processes remain poorly characterized. We previously showed that normal human epidermal keratinocytes ...
Show more >The incidence of carcinomas highly increases with age. However, the initial steps of the age-related molecular carcinogenic processes remain poorly characterized. We previously showed that normal human epidermal keratinocytes spontaneously and systematically escape from senescence to give rise to preneoplastic emerging cells through a process called post-senescence neoplastic emergence (PSNE). To identify molecular pathways involved in the switch from senescence to pre-transformation, we performed Connectivity Map analyses and DAVID functional annotations followed by hierarchical clustering and multidimensional scaling of the gene expression signature of PSNE cells. We identified endoplasmic reticulum stress related pathways as key regulators of PSNE. Invalidation by RNA interference of the UPR sensors PERK, ATF6α, but not IRE1α, delayed the occurrence of senescence when performed in pre-senescent cells, and increased the PSNE frequency when performed in already senescent cells. Conversely, endoplasmic reticulum stress inducers applied to already senescent cells decreased the frequency of PSNE. In conclusion, these results indicate that the activation of the UPR could protect from the early carcinogenic steps by senescence evasion. This opens new avenues to explore therapeutics that could be useful in decreasing the age-associated tumor incidence.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
CNRS
Université de Lille

Collections :

• Mécanismes de la Tumorigénèse et Thérapies Ciblées (M3T) - UMR 8161
• METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694

Submission date :

2019-12-09T18:19:29Z