RT Journal Article
SR Electronic
T1 Injury suppresses Ras cell competitive advantage through enhanced wild-type cell proliferation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.05.475078
DO 10.1101/2022.01.05.475078
A1 Sara Gallini
A1 Nur-Taz Rahman
A1 Karl Annusver
A1 David G. Gonzalez
A1 Sangwon Yun
A1 Catherine Matte-Martone
A1 Tianchi Xin
A1 Elizabeth Lathrop
A1 Kathleen C. Suozzi
A1 Maria Kasper
A1 Valentina Greco
YR 2022
UL http://biorxiv.org/content/early/2022/01/06/2022.01.05.475078.abstract
AB Healthy skin is a tapestry of wild-type and mutant clones. Although injury can cooperate with Ras mutations to promote tumorigenesis, the consequences in genetically mosaic skin are unknown. Here, we show that wild-type cells prevent oncogenic Ras-induced aberrant growth after injury. Although HrasG12V/+ and KrasG12D/+ cells outcompete wild-type cells in uninjured, mosaic tissue, their competitive advantage is suppressed after injury due to a selective increase in wild-type cell proliferation. EGFR inhibition abolishes the competitive advantage of wild-type cells after injury of HrasG12V/+-mosaic skin. Global loss of the cell cycle inhibitor p21 increases wild-type cell proliferation even without injury, suppressing the competitive advantage of HrasG12V/+ cells. Thus, injury plays an unanticipated role in switching the competitive balance between oncogenic and wild-type cells in genetically mosaic skin.One sentence Summary Injury-repair selectively induces wild-type cell proliferation to suppress oncogenic growth in Ras-mosaic skin epithelium.Competing Interest StatementThe authors have declared no competing interest.