Open AccessSTAT3 Is Required for Proliferation and Maintenance of Multipotency in Glioblastoma Stem Cells
Author(s) -
Sherry Maureen M.,
Reeves Andrew,
Wu Julian K.,
Cochran Brent H.
Publication year - 2009
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.185
Subject(s) - neurosphere , biology , stat3 , neural stem cell , stem cell , microbiology and biotechnology , cancer stem cell , stat protein , cell growth , cancer research , carcinogenesis , cellular differentiation , signal transduction , adult stem cell , cancer , genetics , gene
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. STEM CELLS 2009;27:2383–2392