Affiliation:
1. Department of Neurosurgery Tianjin Medical University General Hospital. Tianjin Neurological Institute, Laboratory of Neuro‐Oncology, Key Laboratory of Post‐Trauma Neuro‐Repair and Regeneration in Central Nervous System, Ministry of Education. Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System Tianjin P. R. China
2. Clinical College of Neurology Neurosurgery and Neurorehabilitation Tianjin Medical University Tianjin P. R. China
3. Laboratory of Neuro‐Chemistry Tianjin Neurological Institute, Tianjin Medical University General Hospital Tianjin China
4. Department of Neurosurgery Tianjin Huanhu Hospital Tianjin China
Abstract
AbstractPKN1 (protein kinase N1), a serine/threonine protein kinase family member, is associated with various cancers. However, the role of PKN1 in gliomas has rarely been studied. We suggest that PKN1 expression in glioma specimens is considerably upregulated and positively correlates with the histopathological grading of gliomas. Knocking down PKN1 expression in glioblastoma (GBM) cells inhibits GBM cell proliferation, invasion and migration and promotes apoptosis. In addition, yes‐associated protein (YAP) expression, an essential effector of the Hippo pathway contributing to the oncogenic role of gliomagenesis, was also downregulated. In contrast, PKN1 upregulation enhances the malignant characteristics of GBM cells and simultaneously upregulates YAP expression. Therefore, PKN1 is a promising therapeutic target for gliomas. Raloxifene (Ralo), a commonly used selective oestrogen‐receptor modulator to treat osteoporosis in postmenopausal women, was predicted to target PKN1 according to the bioinformatics team from the School of Mathematics, Tianjin Nankai University. We showed that Ralo effectively targets PKN1, inhibits GBM cells proliferation and migration and sensitizes GBM cells to the major chemotherapeutic drug, Temozolomide. Ralo also reverses the effect of PKN1 on YAP activation. Thus, we confirm that PKN1 contributes to the pathogenesis of gliomas and may be a potential target for Ralo adjuvant glioma therapy.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Tianjin City
Subject
Cell Biology,Molecular Medicine