We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Genome-wide CRISPR screens of oral squamous cell carcinoma reveal fitness genes in the Hippo pathway.
- Authors
Annie Wai Yeeng Chai; Pei San Yee; Price, Stacey; Shi Mun Yee; Hui Mei Lee; Tiong, Vivian K. H.; Gonçalves, Emanuel; Behan, Fiona M.; Bateson, Jessica; Gilbert, James; Tan, Aik Choon; McDermott, Ultan; Garnett, Mathew J.; Sok Ching Cheong
- Abstract
New therapeutic targets for oral squamous cell carcinoma (OSCC) are urgently needed. We conducted genome-wide CRISPR-Cas9 screens in 21 OSCC cell lines, primarily derived from Asians, to identify genetic vulnerabilities that can be explored as therapeutic targets. We identify known and novel fitness genes and demonstrate that many previously identified OSCC-related cancer genes are non30 essential and could have limited therapeutic value, while other fitness genes warrant further investigation for their potential as therapeutic targets. We validate a distinctive dependency on YAP1 and WWTR1 of the Hippo pathway, where the lost of-fitness effect of one paralog can be compensated only in a subset of lines. We also discover that OSCCs 34 with WWTR1 dependency signature are significantly associated with biomarkers of favourable response towards immunotherapy. In summary, we have delineated the genetic vulnerabilities of OSCC, enabling the prioritization of therapeutic targets for further exploration, including the targeting of YAP1 and WWTR1.
- Subjects
SQUAMOUS cell carcinoma; CRISPRS; CANCER genes; GENOME editing; GENES; CELL lines
- Publication
eLife, 2020, p1
- ISSN
2050-084X
- Publication type
Article