P05 Yes-associated protein engages RIF1 to dampen replication stress-induced DNA damage in squamous cell carcinoma
Clicks: 2
ID: 318370
2026
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This
article has not been analysed, so there is no overall score —
reader engagement is measured and shown alongside.
Reader Engagement
Steady Performance
0.3
/100
2 views
1 readers
AI Quality Assessment
Not analyzed
Readership in this journal
SteadyRanked #183 of 304 articles by views in the british journal of dermatology
Most read
Least read
Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 304 in total.
Mint this article as an NFT
Not yet mintedCreate a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.
5
SUSD
one-off · no wallet required
Abstract
Abstract Introduction and aims Squamous cell carcinomas (SCCs) are among the most common solid tumours, with cutaneous SCC being the most prevalent type, imposing a major healthcare burden owing to its high incidence. Head and neck SCC (HNSCC) is less frequent; however, it has a higher mortality rate. SCC cells undergo high levels of replication stress owing to oncogene-induced cell cycle deregulation. How such cells sustain rapid proliferation despite replication stress is still not fully understood. The transcriptional coregulators Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ, also known as WWTR1) are critical oncoproteins in SCC. In fact, ∼50% of patients with HNSCC harbour somatic alterations in components of the regulatory Hippo signalling pathway or YAP1/WWTR1 copy number gains, which invariably lead to hyperactivation of YAP/TAZ. How YAP/TAZ control oncogenic signalling in human SCC at the molecular level, and how human SCC cells deal with YAP/TAZ-induced replication stress remains poorly understood. Methods Using a multiomics approach involving RNA sequencing and chromatin-immunoprecipitation coupled with mass spectrometry, and combined with various molecular cell biology techniques, we have characterized transcriptional and nontranscriptional mechanisms of the oncogenic functions of YAP in human cutaneous SCC and HNSCC cell lines. Results We identified RIF1, a key regulator of DNA replication and DNA damage repair under replication stress, as an important binding partner of YAP in human SCC cells. RIF1 is highly expressed in human SCC cell lines and tissues and upregulated during tumour progression. Depletion of RIF1 in SCC cells exacerbates their endogenous replication stress. Mechanistically, we show that YAP engages with RIF1 specifically at broken replication forks, and that YAP depletion impairs DNA damage repair under replication stress. Conclusions Our results demonstrate that the oncogenic functions of YAP in squamous cancers involve both transcriptional and nontranscriptional mechanisms, the latter through interaction with RIF1 to dampen replication stress.
| Reference Key |
openalex_W7165627644
Use this key to autocite in the manuscript while using
SciMatic Manuscript Manager or Thesis Manager
|
|---|---|
| Authors | Jodie Bojko, Elodie Sins, Benjamin Flynn, James Scarth, Mikal Negasi, Bertram Aschenbrenner, Molly Guscott, Alexander Howard, Emily Lay, Emma Bailey, Natalia Krajic, Marco Franciosi, Sandra Catalan Jimenez, Kelli Gallacher, Ilaria di Girolamo, Reem Bagabas, Caterina Missero, Jun Wang, Sarah McClelland, B M Lichtenberger, Ute Jungwirth, Gernot Walko |
| Journal | the british journal of dermatology |
| Year | 2026 |
| DOI |
10.1093/bjd/ljag151.046
|
| URL | |
| Keywords | Keywords not found |
Citations
No citations found. To add a citation, contact the admin at info@scimatic.org
Comments
No comments yet. Be the first to comment on this article.