Unknown

Dataset Information

0

Characterization of a Steroid Receptor Coactivator Small Molecule Stimulator that Overstimulates Cancer Cells and Leads to Cell Stress and Death.


ABSTRACT: By integrating growth pathways on which cancer cells rely, steroid receptor coactivators (SRC-1, SRC-2, and SRC-3) represent emerging targets in cancer therapeutics. High-throughput screening for SRC small molecule inhibitors (SMIs) uncovered MCB-613 as a potent SRC small molecule "stimulator" (SMS). We demonstrate that MCB-613 can super-stimulate SRCs' transcriptional activity. Further investigation revealed that MCB-613 increases SRCs' interactions with other coactivators and markedly induces ER stress coupled to the generation of reactive oxygen species (ROS). Because cancer cells overexpress SRCs and rely on them for growth, we show that we can exploit MCB-613 to selectively induce excessive stress in cancer cells. This suggests that over-stimulating the SRC oncogenic program can be an effective strategy to kill cancer cells.

SUBMITTER: Wang L 

PROVIDER: S-EPMC4536575 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

Characterization of a Steroid Receptor Coactivator Small Molecule Stimulator that Overstimulates Cancer Cells and Leads to Cell Stress and Death.

Wang Lei L   Yu Yang Y   Chow Dar-Chone DC   Yan Fei F   Hsu Chih-Chao CC   Stossi Fabio F   Mancini Michael A MA   Palzkill Timothy T   Liao Lan L   Zhou Suoling S   Xu Jianming J   Lonard David M DM   O'Malley Bert W BW  

Cancer cell 20150801 2


By integrating growth pathways on which cancer cells rely, steroid receptor coactivators (SRC-1, SRC-2, and SRC-3) represent emerging targets in cancer therapeutics. High-throughput screening for SRC small molecule inhibitors (SMIs) uncovered MCB-613 as a potent SRC small molecule "stimulator" (SMS). We demonstrate that MCB-613 can super-stimulate SRCs' transcriptional activity. Further investigation revealed that MCB-613 increases SRCs' interactions with other coactivators and markedly induces  ...[more]

Similar Datasets

| S-EPMC9751323 | biostudies-literature
| S-EPMC7733826 | biostudies-literature
2020-09-06 | GSE157542 | GEO
| S-EPMC3990629 | biostudies-literature
| S-EPMC2820291 | biostudies-literature
| S-EPMC6645384 | biostudies-literature
| S-EPMC2582912 | biostudies-literature
| S-EPMC2921768 | biostudies-literature
| S-EPMC2998129 | biostudies-literature
| S-EPMC4280633 | biostudies-literature