Glioblastoma is the most common and lethal primary intracranial tumor. As the key regulator of tumor cell volume, sodium‐potassium‐chloride cotransporter 1 (NKCC1) expression increases along with the malignancy of the glioma, and NKCC1 has been implicated in glioblastoma invasion. However, little is known about the role of NKCC1 in the epithelial‐mesenchymal transition‐like process in gliomas. We noticed that aberrantly elevated expression of NKCC1 leads to changes in the shape, polarity, and adhesion of cells in glioma. Here, we investigated whether NKCC1 promotes an epithelial–mesenchymal transition (EMT)‐like process in gliomas via the RhoA and Rac1 signaling pathways. Pharmacological inhibition and knockdown of NKCC1 both decrease the expressions of mesenchymal markers, such as N‐cadherin, vimentin, and snail, whereas these treatments increase the expression of the epithelial marker E‐cadherin. These findings indicate that NKCC1 promotes an EMT‐like process in gliomas. The underlying mechanism is the facilitation of the binding of Rac1 and RhoA to GTP by NKCC1, which results in a significant enhancement of the EMT‐like process. Specific inhibition or knockdown of NKCC1 both attenuate activated Rac1 and RhoA, and the pharmacological inhibitions of Rac1 and RhoA both impair the invasion and migration abilities of gliomas. Furthermore, we illustrated that NKCC1 knockdown abolished the dissemination and spread of glioma cells in a nude mouse intracranial model. These findings suggest that elevated NKCC1 activity acts in the regulation of an EMT‐like process in gliomas, and thus provides a novel therapeutic strategy for targeting the invasiveness of gliomas, which might help to inhibit the spread of malignant intracranial tumors.

Numerous studies have shown that calmodulin (CaM) is a major regulator of calcium-dependent signaling, which regulates cell proliferation, programmed cell death, and autophagy in cancer. However, limited information is available on mechanisms underlying the effect of CaM on the invasive property of glioblastoma multiforme (GBM) cells, especially with respect to invadopodia formation. In this study, we find that CaM serves as a prognostic factor for GBM, and it is strongly associated with the invasive nature of this tumor. Results of preliminary experiments indicated that CaM concentration was significantly correlated with the invasive capacity of and invadopodia formation by different GBM cell lines. CaM inhibition via a small hairpin RNA or a pharmacological inhibitor significantly disrupted invadopodia formation and MMP activity and downregulated vimentin expression. Moreover, CaM knockdown exerted a strong anti-invasive effect on GBM in vivo. Interestingly, epidermal growth factor treatment promoted CaM redistribution from the nucleus to the cytoplasm, eventually activating invadopodia-associated proteins by binding to them via their cytosolic-binding sites. Moreover, CaM inhibition suppressed the activation of invadopodia-associated proteins. Thus, our findings provide a novel therapeutic strategy to impede GBM invasion by inhibiting invadopodia formation, and shed light on the spatial organization of CaM signals during GBM invasion.

Wistar rats were randomly divided into groups of varying iodide intake: normal iodide; 10 times high iodide; and 100 times high iodide on Days 7, 14, and 28. Insignificant changes were observed in thyroid hormone levels (p > 0.05). Urinary iodine concentration and iodine content in the thyroid glands increased after high consumption of iodide from NI to 100 HI (p < 0.05). The urinary iodine concentration of the 100 HI group on Days 7, 14, and 28 was 60–80 times that of the NI group. The mitochondrial superoxide production and expressions of Nrf2, Srx, and Prx 3 all significantly increased, while Keap 1 significantly decreased in the 100 HI group when compared to the NI or 10 HI group on Days 7, 14, and 28 (p < 0.05). Immunofluorescence staining results showed that Nrf2 was localized in the cytoplasm in NI group. Although Nrf2 was detected in both cytoplasm and nucleus in 10 HI and 100 HI groups, a stronger positive staining was found in the nucleus. We conclude that the activation of the Nrf2-Keap 1 antioxidative defense mechanism may play a crucial role in protecting thyroid function from short-term iodide excess in rats.

Glioblastoma multiforme (GBM) is one of the most lethal types of tumour, despite severe treatment methods. The Cancer Genome Atlas has categorised GBMs into proneural, neural, classical and mesenchymal subtypes; the mesenchymal subgroup has the worst prognosis. CXCR4 has been reported as selectively overexpressed in the mesenchymal subtype and positively associated with MES markers. However, to the best of our knowledge the underlying mechanisms regarding how CXCR4 may regulate mesenchymal GBM are still unknown. The present study aimed to investigate the critical pathways mediated by CXCR4 in mesenchymal GBM using bioinformatic analyses. The results suggested that CXCR4 is a predictor of poor prognosis and may serve as a biomarker of the mesenchymal subtype in patients with GBM. In addition, CXCR4 mediated the mitogen-activated protein kinase signaling pathway, which was identified specifically in patients with mesenchymal GBM. CXCR4 associated genes or pathways may be a ‘basket trial’ option for the management of melanoma, prostate cancer and mesenchymal GBM.