Searching the Resource Information Network
Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.
Chemotherapy is designed to induce cell death. However, at non-lethal doses, cancer cells can choose to remain proliferative or become senescent. The slow development of senescence makes studying this decision challenging. Here, by analyzing single-cell p21 dynamics before, during, and days after drug treatment, we link three distinct patterns of early p21 dynamics to final cell fate. Surprisingly, while high p21 expression is classically associated with senescence, we find the opposite at early times during drug treatment: most senescence-fated cells express much lower p21 levels than proliferation-fated cells. We demonstrate that these dynamics lead to a p21 "Goldilocks zone" for proliferation, in which modest increases of p21 expression can lead to an undesirable increase of cancer cell proliferation. Our study identifies a counter-intuitive role for early p21 dynamics in the cell-fate decision and pinpoints a source of proliferative cancer cells that can emerge after exposure to non-lethal doses of chemotherapy.
Pubmed ID: 31204100
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This monoclonal targets Histone H2A.X, phospho (Ser139)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets Mouse IgG (H+L)
View all literature mentionsThis monoclonal targets Phospho-Rb (Ser807/811) (D20B12) XP Rabbit mAb
View all literature mentionsThis unknown targets Goat IgG (H+L)
View all literature mentionsThis polyclonal targets beta Tubulin antibody - Loading Control
View all literature mentionsThis monoclonal targets p53 (1C12) Mouse mAb
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets c-Myc (D84C12) XP Rabbit mAb
View all literature mentionsThis monoclonal targets gamma H2A.X (phospho S139) antibody [9F3]
View all literature mentionsThis monoclonal targets p21 Waf1/Cip1
View all literature mentionsThis monoclonal targets Skp2 (D3G5) XP Rabbit mAb
View all literature mentions