Glioma is the most common type of malignant intracranial tumor in adults and is associated with the highest mortality rate. Although surgery, radiotherapy, chemotherapy and other treatment methods have progressed, the median survival of patients with glioma is only 14–15 months. Glioma cells are able to penetrate along blood vessels and invade into the surrounding normal brain tissue so that an overall resection of the tumor cannot be performed. In the process of metastasis, the resistance of cancer cells to anoikis has an important role. When tumor cells escape from their original environment, anoikis resistance aids their survival. In the present study, reverse transcription-semi-quantitative polymerase chain reaction (RT-sqPCR), RT-quantitative PCR and western blotting demonstrated that the transcription factor, motor neuron and pancreas homeobox 1 (MNX1), was ectopically expressed in glioma cells compared with normal HUVEC-C human umbilical vein endothelial cells. Furthermore, its expression was higher in more malignant glioma cell lines (T98G and M059K) compared with the less malignant glioma cell line (U-87 MG) and normal HUVEC-C cells. An adhesion assay using fibronectin demonstrated that MNX1 and tyrosine kinase receptor B (TrkB) overexpression in HUVEC-C and U-87 MG cells reduced adhesion and forced them to suspend. Additionally, MNX1 and TrkB overexpression was demonstrated to increase the ability of cells to bypass anoikis. MNX1 and TrkB knockdown increased adhesion and promoted apoptosis after suspension. It was further demonstrated that MNX1 functioned as a transcription factor binding in the upstream regulatory region of TrkB to activate its expression. The results of the present study suggested that MNX1 may suppress the adhesion and apoptosis rates of tumor cells by activating TrkB. The results of the present study suggest that MNX1 may represent a novel therapeutic target for the treatment of gliomas.

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Pancreatic cancer is one of the most aggressive and lethal malignancies with extremely poor prognosis, and KLK7 was considered as a potential therapeutic target. In this study, we analyzed the expression of KLK7 in TCGA and GTEx databases and found that KLK7 had a negative correlation to long-term survival rate (>1.5 years) of pancreatic cancer patients. Compound 42 is a coumarinic derivative, a suicide substrate inhibitor of KLK7, which has been proved to inhibit the proliferation of PANC-1 cells in vitro effectively in our previous study. In this study, we further investigated the inhibition ability of Compound 42 in tumor formation and development in CDX and PDX tumor models of pancreatic cancer subsequently. Besides, we studied the inhibitory mechanism of Compound 42 and the result showed that Compound 42 arrested the pancreatic cancer cell cycle in G0/G1 phase and induced ferroptosis through down-regulation of GPX4 protein level and accumulation of iron ion. Thus, these experiments demonstrate that Compound 42, suppressing pancreatic cancer in vivo, is expected to become a novel drug for pancreatic cancer treatment.