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The small molecule ID8 increases Aldefluor+ breast cancer stem cells

ABSTRACT: The cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self-renewing CSC population that is also capable of differentiating into non-self renewing cell populations that constitute the bulk of the tumor. Targeting breast CSC (BCSC) self-renewal represents an avenue for developing therapeutics; however, the molecular mechanisms that govern self-renewal of BCSCs are poorly understood. Our data show the small molecule ID8 decreases overall cell growth, but increases the self-renewal of Aldefluor+ BCSCs and increases functional metastatic BCSCs in a xenograft model. Microarray analysis showed that ID8 is a pleotropic molecule by increasing numerous pathways, including cytokines and chemokines. However, inhibition of those pathways does not abrogate the ID8-induced increase in Aldefluor+ BCSCs. Rather, ID8 is able to activate MAPK pathway through upregulation of the scaffold protein LAMTOR3 and inhibition of MEK prevented the increase in Aldefluor+ BCSCs. By using ID8 as a molecular tool, we identified a new function of the MAPK pathway in regulating BCSC growth and self-renewal.

ORGANISM(S): Homo sapiens

PROVIDER: GSE80213 | GEO | 2016/11/01

SECONDARY ACCESSION(S): PRJNA318286

REPOSITORIES: GEO

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2020-08-25 | E-MTAB-5393 | biostudies-arrayexpress

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2020-01-06 | E-MTAB-8140 | biostudies-arrayexpress

breast cancer cell lines ALDH+/-

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2015-01-01 | E-MTAB-2236 | biostudies-arrayexpress

ID8 whole exome sequence

Project description:ID8 whole exome sequence

| PRJEB13730 | ENA

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