Id |
Subject |
Object |
Predicate |
Lexical cue |
T1 |
0-95 |
Sentence |
denotes |
FOXO3 growth inhibition of colonic cells is dependent on intraepithelial lipid droplet density. |
T2 |
96-320 |
Sentence |
denotes |
Forkhead transcription factor FOXO3 plays a critical role in suppressing tumor growth, in part, by increasing the cell cycle inhibitor p27kip1, and Foxo3 deficiency in mice results in marked colonic epithelial proliferation. |
T3 |
321-501 |
Sentence |
denotes |
Here, we show in Foxo3-deficient colonic epithelial cells a striking increase in intracytoplasmic lipid droplets (LDs), a dynamic organelle recently observed in human tumor tissue. |
T4 |
502-739 |
Sentence |
denotes |
Although the regulation and function of LDs in non-adipocytes is unclear, we hypothesize that the anti-proliferative effect of FOXO3 was dependent on lowering LD density, thus decreasing fuel energy in both normal and colon cancer cells. |
T5 |
740-869 |
Sentence |
denotes |
In mouse colonic tumors, we found an increased expression of LD coat protein PLIN2 compared with normal colonic epithelial cells. |
T6 |
870-1043 |
Sentence |
denotes |
Stimulation of LD density in human colon cancer cells led to a PI3K-dependent loss of FOXO3 and a decrease in the negative regulator of lipid metabolism in Sirtuin6 (SIRT6). |
T7 |
1044-1171 |
Sentence |
denotes |
Foxo3 deficiency also led to a decrease in SIRT6, revealing the existence of LD and FOXO3 feedback regulation in colonic cells. |
T8 |
1172-1315 |
Sentence |
denotes |
In parallel, LD-dependent loss of FOXO3 led to its dissociation from the promoter and decreased expression of the cell cycle inhibitor p27kip1. |
T9 |
1316-1463 |
Sentence |
denotes |
Stimulation of LD density promoted proliferation in colon cancer cells, whereas silencing PLIN2 or overexpression of FOXO3 inhibited proliferation. |
T10 |
1464-1566 |
Sentence |
denotes |
Taken together, FOXO3 and LDs might serve as new targets for therapeutic intervention of colon cancer. |