2012
DOI: 10.1038/onc.2012.137
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Suppression of proinvasive RGS4 by mTOR inhibition optimizes glioma treatment

Abstract: An essential mode of acquired resistance to radiotherapy (RT) appears to be promotion of tumor cell motility and invasiveness in various cancer types, including glioblastoma, a process resembling 'evasive resistance'. Hence, a logical advancement of RT would be to identify suitable complementary treatment strategies, ideally targeting cell motility. Here we report that the combination of focal RT and mammalian target of rapamycin (mTOR) inhibition using clinically relevant concentrations of temsirolimus (CCI-7… Show more

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Cited by 36 publications
(40 citation statements)
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“…We found 91 genes downregulated by SMAD4 expression at 8h including a number of novel targets. A few notable examples include interleukin 1 receptor-like 1 (IL1RL1; 0.403x at 8h), a candidate driver of inflammation-associated pancreatic carcinogenesis (48); regulator of G-protein signaling 4 (RGS4; 0.293x at 8h), a regulator of G-protein signaling implicated in regulation of migration and invasion (49,50); and THAP domain containing 11 (THAP11; 0.262x at 8h), a transcriptional regulator overexpressed in colon cancer that may have progrowth effects in cancer (51). The regulation of these genes within hours of SMAD4 expression suggests that they may be direct targets and future studies are needed to address the role of TGF-␤-signaling in their regulation.…”
Section: Discussionmentioning
confidence: 99%
“…We found 91 genes downregulated by SMAD4 expression at 8h including a number of novel targets. A few notable examples include interleukin 1 receptor-like 1 (IL1RL1; 0.403x at 8h), a candidate driver of inflammation-associated pancreatic carcinogenesis (48); regulator of G-protein signaling 4 (RGS4; 0.293x at 8h), a regulator of G-protein signaling implicated in regulation of migration and invasion (49,50); and THAP domain containing 11 (THAP11; 0.262x at 8h), a transcriptional regulator overexpressed in colon cancer that may have progrowth effects in cancer (51). The regulation of these genes within hours of SMAD4 expression suggests that they may be direct targets and future studies are needed to address the role of TGF-␤-signaling in their regulation.…”
Section: Discussionmentioning
confidence: 99%
“…To silence NDRG1 gene expression, two short-hairpin RNA (shRNA) sequences targeting different sites were cloned into the pSUPER-puro vector (11,12). The sequences are provided in SI Appendix.…”
Section: Methodsmentioning
confidence: 99%
“…Preparation of cell lysates and immunoblots were performed as described before (12). Antibodies are given in SI Appendix, ).…”
Section: Methodsmentioning
confidence: 99%
“…Hybrid visualization of HGG presenting angiogenic characteristics vs. other mainly infiltrative characteristics will guide the boost for dose-painting and will potentially determine whether concomitant treatment with antiangiogenic and/or antiinvasiveness drugs are needed[49]. Of note, the first PET/MRI machines are available now, and HGG could be a good model[50].…”
Section: Next Steps: Combination Homogeni-zation Adaptation and Inmentioning
confidence: 99%