Glioblastoma (GBM) is a highly infiltrative and malignant primary brain tumor. Despite aggressive therapy, patients with GBM have a dismal prognosis with median survival of approximately 1 year. Tamoxifen (TAM), a selective estrogen receptor modulator (SERM), has been used to treat GBM for many years. ER‐α36 is a novel variant of estrogen receptor‐alpha66 (ER‐α66) and can mediate cell proliferation through estrogen or anti‐estrogen signaling in different cancer cells. Previously, we found that ER‐α36 was highly expressed in GBM and was involved in the tamoxifen sensitivity of glioblastoma cells. However, the molecular mechanism responsible has not been well established. Here, we found that ER‐α36 is highly expressed in glioblastoma specimens. We further found that ER‐α36 knockdown increased sensitivity of glioblastoma U87 cells to TAM and decreased autophagy in these cells. However, ER‐α36 overexpression decreased TAM sensitivity and induced autophagy. We also established TAM‐resistant glioblastoma U251 cells by a long‐term culture in TAM‐containing medium and found that TAM‐resistant cells showed a six‐fold increase of ER‐α36 mRNA expression and elevated basal autophagy. ER‐α36 knockdown in these TAM‐resistant cells restored TAM sensitivity. In addition, we recapitulated the physiologically relevant tumor microenvironment in an integrated microfluidic device, and U87 cells were treated with a gradient of TAM. We found that ER‐α36 expression is consistent with autophagy protein P62 in a three‐dimensional microenvironment. In summary, these results indicate that ER‐α36 contributes to tamoxifen resistance in glioblastoma cells presumably through regulation of autophagy.

K⁺ channels regulate a multitude of biological processes and play important roles in a variety of diseases by controlling potassium flow across cell membranes. They are widely expressed in the central and peripheral nervous system. As a malignant tumor derived from nerve epithelium, glioma has the characteristics of high incidence, high recurrence rate, high mortality rate, and low cure rate. Since glioma cells show invasive growth, current surgical methods cannot completely remove tumors. Adjuvant chemotherapy is still needed after surgery. Because the blood-brain barrier and other factors lead to a lower effective concentration of chemotherapeutic drugs in the tumor, the recurrence rate of residual lesions is extremely high. Therefore, new therapeutic methods are needed. Numerous studies have shown that different K⁺ channel subtypes are differentially expressed in glioma cells and are involved in the regulation of the cell cycle of glioma cells to arrest them at different stages of the cell cycle. Increasing evidence suggests that K⁺ channels express in glioma cells and regulate glioma cell behaviors such as cell cycle, proliferation and apoptosis. This review article aims to summarize the current knowledge on the function of K⁺ channels in glioma, suggests K⁺ channels participating in the development of glioma.

The neuroprotection by estrogen (E2) and tamoxifen is well documented in experimental stroke models; however, the exact mechanism is unclear. A membrane-based estrogen receptor, ER-α36, has been identified. Postmenopausal-levels of E2 act through ER-α36 to induce osteoclast apoptosis due to a prolonged activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) signaling. We hypothesized that ER-α36 may play a role in the neuroprotective activities of estrogen and tamoxifen. Here, we studied ER-α36 expression in the brain, as well as its neuroprotective effects against oxygen and glucose deprivation (OGD) in PC12 cells. We found that ER-α36 was expressed in both rat and human brain. In addition, OGD-induced cell death was prevented by l nmol/L 17β-estradiol (E2β). E2β activates the MAPK/ERK signaling pathway in PC12 cells under basal and OGD conditions by interacting with ER-α36 and also induces ER-α36 expression. Low-dose of tamoxifen up-regulated ER-α36 expression and enhanced neuronal survival in an ovariectomized ischemic stroke model. Furthermore, low-dose of tamoxifen enhanced neuroprotective effects by modulating activates or suppress ER-α36. Our results thus demonstrated that ER-α36 is involved in neuroprotective activities mediated by both estrogen and tamoxifen.

Human adipose‑derived stem cells (hADSCs), widely present in the adult human body, are an emerging and attractive tool for the establishment of stem cell‑based therapies for the treatment of liver disease. However, the mechanism underlying hADSCs hepatic differentiation remains to be elucidated. Caveolin‑1 (Cav‑1), a 21‑24 kDa membrane structural protein, is important in liver regeneration and development. In the present study, fluorescence immunocytochemistry and western blotting were used to analyze the expression levels of Cav‑1 and evaluate its effects on the hepatic differentiation of hADSCs. The results revealed that primary hADSCs preserved the ability to proliferate and differentiate into hepatocyte‑like cells. As demonstrated by semiquantitative reverse transcription‑polymerase chain reaction, hepatocyte‑inducing factors significantly increased the expression of Cav‑1 in a time‑dependent manner, as indicated by increased expression levels of the albumin (ALB) and α‑fetoprotein (AFP) markers. In addition the expression levels of ALB and HNF1A significantly decreased following small interfering RNA‑mediated knockdown of Cav‑1. The mitogen‑activated protein kinase (MAPK) signaling pathway was activated during hepatic differentiation and inhibited following Cav‑1 knockdown. These results suggested that Cav‑1 may regulate the hepatocyte‑like differentiation of hADSCs by modulating mitogen‑activated protein kinase kinase/MAPK signaling. The results of the present study will provide experimental and theoretical basis for further clinical studies on stem cell transplantation in the treatment of liver disease.