Wnt/β-catenin signaling is a key downstream mediator of MET signaling in glioblastoma stem cells

Background

Glioblastoma (GBM) is the most lethal and common type of primary brain tumor. Recent evidence suggests that a subpopulation of GBM cells (glioblastoma stem cells [GSCs]) is critical for tumor progression, invasion, and therapeutic resistance. We and others have demonstrated that MET, a receptor tyrosine kinase, positively regulates the stemness phenotype and radioresistance of GSCs. Here, we interrogated the downstream effector pathways of MET signaling in GSCs.

Methods

We have established a series of GSCs and xenograft tumors derived from freshly dissociated specimens from patients with GBM and characterized a subpopulation enriched with MET activation (MET^high/+). Through global expression profiling and subsequent pathways analysis, we identified signaling pathways that are enriched in MET^high/+ populations, one of which is Wnt/β-catenin signaling pathway. To determine molecular interaction and the biological consequences of MET and Wnt/β-catenin signaling, we used pharmacological and shRNA-mediated genetic inhibition and performed various molecular and cellular analyses, including flow cytometry, immunohistochemistry, and clonogenicity assays.

Results

We found that Wnt/β-catenin signaling is highly active in MET^high/+ cells, compared with bulk tumor cells. We also showed that Wnt/β-catenin signaling activities in GBM are directly modulated by the addition of ligand-mediated MET activation or MET inhibition. Furthermore, the ectopic expression of active-β-catenin (S37A and S45Y) rescued the phenotypic effects caused by MET inhibition.

Conclusion

These data suggest that Wnt/β-catenin signaling is a key downstream effector of MET signaling and contributes to the maintenance of GSC and GBM malignancy.     

BP1 transcriptionally activates bcl-2 and inhibits TNFα-induced cell death in MCF7 breast cancer cells

Introduction  

We have previously shown that the Beta Protein 1 (BP1) homeodomain protein is expressed in 81% of invasive ductal breast carcinomas, and that increased BP1 expression correlates with tumor progression. The purpose of our current investigation was to determine whether elevated levels of BP1 in breast cancer cells are associated with increased cell survival.     

鼻内镜下Hasner瓣切除术治疗低位鼻泪管阻塞的临床研究

目的探讨Hasner瓣切除术用于低位鼻泪管阻塞患者治疗的临床效果。 方法收集2016年10月至2019年1月于首都医科大学附属北京同仁医院北京同仁眼科中心进行Hasner瓣切除术患者31例(31只眼)的病例资料。其中，男性3例，女性28例；年龄17~79岁，平均年龄(41.8±15.5)岁。观察术前与术后溢泪症状、泪河高度(TMH)及泪道冲洗检查结果的情况。采用配对样本t检验比较同一患眼术前与术后TMH值的变化、不同观察时间点TMH差值的变化；采用Wilcoxon符号秩和检验比较术前与术后泪道的冲洗检查结果。 结果患眼Hasner瓣切除术后90%无溢泪，10%溢泪有所减轻。术前患眼染色前TMH值为(0.62±0.32)mm，术后患眼染色前TMH值为(0.30±0.10)mm，差异有统计学意义(t＝5.25, P<0.05)。患眼术前与术后在染色后0 min和染色后5 min的TMH值变化明显，差异有统计学意义(t＝2.31，5.45；P<0.05)；而健眼术前与术后在染色前、染色后0 min及染色后5 min的TMH值变化，差异无统计学意义(t＝0.40，-0.25，0.25；P>0.05)。健眼术前染色后0 min与染色前的TMH差值为(0.17±0.17)mm；术前染色后0 min与染色后5 min的TMH差值为(0.12±0.19)mm。患眼术前染色后0 min与染色前的TMH差值为(0.02±0.27)mm；术前染色后0 min与染色后5 min的TMH差值为(-0.14±0.28)mm。患眼术前与术后在不同观察时间点的TMH差值均有统计学意义(t＝-3.90，-4.69；P<0.05)。健眼术前与术后在不同观察时间点的TMH差值均无统计学意义(t＝-0.13，-0.61；P>0.05)。术前患眼的泪道冲洗检查结果为1或者2者占96%；术后患眼的冲洗检查结果为6者占90.4%，差异有统计学意义(Z＝-4.02，P<0.05)。 结论Hasner瓣切除术用于低位鼻泪管阻塞患者的治疗有较好的治疗效果，术后患者的泪道通畅程度能显著得到改善。