MOB2 suppresses GBM cell migration and invasion via regulation of FAK/Akt and cAMP/PKA signaling

Abstract

Mps one binder 2 (MOB2) regulates the NDR kinase family, however, whether and how it is implicated in cancer remain unknown. Here we show that MOB2 functions as a tumor suppressor in glioblastoma (GBM). Analysis of MOB2 expression in glioma patient specimens and bioinformatic analyses of public datasets revealed that MOB2 was downregulated at both mRNA and protein levels in GBM. Ectopic MOB2 expression suppressed, while depletion of MOB2 enhanced, the malignant phenotypes of GBM cells, such as clonogenic growth, anoikis resistance, and formation of focal adhesions, migration, and invasion. Moreover, depletion of MOB2 increased, while overexpression of MOB2 decreased, GBM cell metastasis in a chick chorioallantoic membrane model. Overexpression of MOB2-mediated antitumor effects were further confirmed in mouse xenograft models. Mechanistically, MOB2 negatively regulated the FAK/Akt pathway involving integrin. Notably, MOB2 interacted with and promoted PKA signaling in a cAMPdependent manner. Furthermore, the cAMP activator Forskolin increased, while the PKA inhibitor H89 decreased, MOB2 expression in GBM cells. Functionally, MOB2 contributed to the cAMP/PKA signaling-regulated inactivation of FAK/Akt pathway and inhibition of GBM cell migration and invasion. Collectively, these findings suggest a role of MOB2 as a tumor suppressor in GBM via regulation of FAK/Akt signaling. Additionally, we uncover MOB2 as a novel regulator in cAMP/PKA signaling. Given that small compounds targeting FAK and cAMP pathway have been tested in clinical trials, we suggest that interference with MOB2 expression and function may support a theoretical and therapeutic basis for applications of these compounds.

RETRACTED ARTICLE: MYC-mediated upregulation of PNO1 promotes glioma tumorigenesis by activating THBS1/FAK/Akt signaling

“…32 Similarly, high FAK expression and activity in GBM is corrected with poor overall survival. 28,33 Mechanistically, PNO1 interacted with THBS1. Here we provide evidence that PNO1 positively regulated the THBS1/FAK/Akt signaling in GBM cells, which was further confirmed by using individual inhibitors targeting FAK or Akt.…”

“…Coincidentally, the focal adhesion kinase (FAK)/Akt signaling was proved to participate in mediating the inhibition of cell migration and invasion of GBM cells. 28 However, the regulatory molecular mechanism of PNO1 on these pathways have not yet been fully determined. Intriguingly, the CO-IP experiments in this study indicated that THBS1 interacted with PNO1 in U251 cells, which has been reported to be associated with tumor development and progression in several types of cancer.…”

Lipid-Lowering Drug, Fenofibrate Combined with si-HOTAIR Can Effectively Inhibit the Proliferation of Gliomas

“…Most of these signaling pathways have been con rmed by scholars to be involved in the progression of tumors and different degrees of abnormal cell behaviors [12]. Excessive activation of phosphatidylinositol could lead to abnormal cell proliferation, abnormal endocytosis and exocytosis, abnormal cell metastasis and even tumor development [13].…”

HGF/MET Signaling in Malignant Brain Tumors

“…Moreover, upregulation of RTKs such as signal transducer and activator of transcription 3 (STAT3) can affect multiple signaling pathways in GBM [ 89 ]. It has been found that STAT3 and focal adhesion kinase (FAK) have a role in the promotion of GBM cell invasion and migration [ 90 ].…”