PKN1 (
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.