期刊
APOPTOSIS
卷 22, 期 5, 页码 719-729出版社
SPRINGER
DOI: 10.1007/s10495-017-1359-1
关键词
Blebbishields; Cellular transformation; VEGFR2; K-Ras; Sp1
Cancer stem cells are capable of undergoing cellular transformation after commencement of apoptosis through the blebbishield emergency program in a VEGF-VEGFR2-dependent manner. Development of therapeutics targeting the blebbishield emergency program would thus be important in cancer therapy. Specificity protein 1 (Sp1) orchestrates the transcription of both VEGF and VEGFR2; hence, Sp1 could act as a therapeutic target. Here, we demonstrate that CF(3)DODA-Me induced apoptosis, degraded Sp1, inhibited the expression of multiple drivers of the blebbishield emergency program such as VEGFR2, p70S6K, and N-Myc through activation of caspase-3, inhibited reactive oxygen species; and inhibited K-Ras activation to abolish transformation from blebbishields as well as transformation in soft agar. These findings confirm CF(3)DODA-Me as a potential therapeutic candidate that can induce apoptosis and block transformation from blebbishields.
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