Unknown

Dataset Information

0

STAT3 is required for proliferation and maintenance of multipotency in glioblastoma stem cells.


ABSTRACT: Signal transducer and activator of transcription 3 (STAT3) regulates diverse cellular processes, including cell growth, differentiation, and apoptosis, and is frequently activated during tumorigenesis. Recently, putative glioblastoma stem cells (GBM-SCs) were isolated and characterized. These cells can self-renew indefinitely in culture, are highly tumorigenic, and retain the ability to differentiate in culture. We have found that treatment of GBM-SCs with two chemically distinct small molecule inhibitors of STAT3 DNA-binding inhibits cell proliferation and the formation of new neurospheres from single cells. Genetic knockdown of STAT3 using a short hairpin RNA also inhibits GBM-SC proliferation and neurosphere formation, confirming that these effects are specific to STAT3. Although STAT3 inhibition can induce apoptosis in serum-derived GBM cell lines, this effect was not observed in GBM-SCs grown in stem cell medium. Markers of neural stem cell multipotency also decrease upon STAT3 inhibition, suggesting that STAT3 is required for maintenance of the stem-like characteristics of these cells. Strikingly, even a transient inhibition of STAT3 leads to irreversible growth arrest and inhibition of neurosphere formation. These data suggest that STAT3 regulates the growth and self-renewal of GBM-SCs and is thus a potential target for cancer stem cell-directed therapy of glioblastoma multiforme.

SUBMITTER: Sherry MM 

PROVIDER: S-EPMC4391626 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

STAT3 is required for proliferation and maintenance of multipotency in glioblastoma stem cells.

Sherry Maureen M MM   Reeves Andrew A   Wu Julian K JK   Cochran Brent H BH  

Stem cells (Dayton, Ohio) 20091001 10


Signal transducer and activator of transcription 3 (STAT3) regulates diverse cellular processes, including cell growth, differentiation, and apoptosis, and is frequently activated during tumorigenesis. Recently, putative glioblastoma stem cells (GBM-SCs) were isolated and characterized. These cells can self-renew indefinitely in culture, are highly tumorigenic, and retain the ability to differentiate in culture. We have found that treatment of GBM-SCs with two chemically distinct small molecule  ...[more]

Similar Datasets

| S-EPMC4086243 | biostudies-literature
| S-EPMC6495637 | biostudies-literature
| S-EPMC2797394 | biostudies-literature
| S-EPMC5458203 | biostudies-literature
| S-EPMC4868756 | biostudies-literature
| S-EPMC2906804 | biostudies-literature
| S-EPMC7020558 | biostudies-literature
| S-EPMC2042178 | biostudies-literature
| S-EPMC4808020 | biostudies-literature
| S-EPMC8641872 | biostudies-literature