Background: Altered Cl -homeostasis and GABAergic function are associated with nociceptive input hypersensitivity. This study investigated the role of two major intracellular Cl -regulatory proteins, Na + -K + -Cl -cotransporter 1 (NKCC1) and K + -Cl -cotransporter 2 (KCC2), in neuropathic pain following spinal cord injury (SCI).

Glioblastoma (GBM) stem cells (GSC) are a subpopulation of tumor cells that display stem-like characteristics (stemness) and play unique roles in tumor propagation, therapeutic resistance, and tumor recurrence. Therapeutic targets in GSCs are a focus of increasing interest to improve GBM therapy. Here we report that the hyaluronan-mediated motility receptor (HMMR) is highly expressed in GBM tumors, where it supports the self-renewal and tumorigenic potential of GSCs. HMMR silencing impairs GSC self-renewal and inhibits the expression of GSC markers and regulators. Furthermore, HMMR silencing suppresses GSC-derived tumor growth and extends the survival of mice bearing GSC xenografts. Conversely, HMMR overexpression promotes GSC selfrenewal and intracranial tumor propagation. In human GBM tumor specimens, HMMR expression is correlated positively with the expression of stemness-associated markers and regulators. Our findings identify HMMR as a candidate therapeutic target to GSCs as a GBM treatment strategy. Cancer Res; 74(11); 3168-79. Ó2014 AACR.

Background: Cancer cell stemness determines tumor propagation and malignancy by poorly defined mechanisms. Results: The KLF9 transcription factor regulates cell fate and oncogenic pathways by repressing gene transcription in glioblastoma stem cells. Conclusion: KLF9 inhibits glioblastoma cell stemness and tumor growth by directly repressing genes, including ITGA6. Significance: KLF9 and its transcriptional network are potential targets for regulating cancer stem cells and glial malignancies.