UM-164, a Dual Inhibitor of c-Src and p38 MAPK, Suppresses Proliferation of Glioma by Reducing YAP Activity.

UM-164 is a dual inhibitor of c-Src and p38 MAPK, and has been a lead compound for targeting triple-negative breast cancer. UM-164 shows stronger binding to the active sites of Src compared with the conventional Src inhibitor Dasatinib. While Dasatinib has displayed some inhibitory effects on glioma growth in clinical trials, whether UM-164 can suppress glioma growth has not been reported. Here we show that UM-164 suppressed the proliferation, migration and spheroid formation of glioma cells, and induced cell cycle arrest in the G1 phase. Moreover, UM-164 triggered YAP translocation to the cytoplasm and reduced the activity of YAP, as evidenced by a luciferase assay. Accordingly, UM-164 markedly decreased the expression levels of YAP target genes CYR61 and AXL. Importantly, ectopic expression of wild-type YAP or YAP-5SA (YAP constitutively active mutant) could rescue the anti-proliferative effect induced by UM-164. Intriguingly, p38 MAPK appears to play a greater role than Src in UM-164-mediated inhibition of YAP activity. Furthermore, the in vitro anti-glioma effect mediated by UM-164 was confirmed in a xenograft glioma model. Together, these findings reveal a mechanism by which UM-164 suppresses the malignant phenotypes of glioma cells and might provide a rationale for UM-164-based anti-glioma clinical trials.

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

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 cAMP-dependent 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.

A mechanically robust silver nanowire-polydimethylsiloxane electrode based on facile transfer printing techniques for wearable displays.

Silver nanowire (AgNW) networks have attracted considerable attention as transparent electrodes for emerging flexible optoelectronics. However, the transference of such networks onto diverse arbitrary substrates with high conductivity remains a challenge because of the possibility of detaching and sliding occurring at the interface. Therefore, we developed a water-assisted transfer printing method for the fabrication and transfer of an AgNW-polydimethylsiloxane (PDMS) electrode. This innovative approach exhibits a robust ability for thin film transfer onto arbitrary substrates and has highly controlled and nondestructive characteristics. The obtained electrodes exhibited a high ratio of DC conductivity to optical conductivity of 200, a low sheet resistance of 9 Ω sq-1 at 82%, tensile strain (0% to 50%), and flexibility (bending radius of less than 2 mm) without significant loss of conductivity compared with devices fabricated through conventional methods. Furthermore, we demonstrated a novel textile-based flexible light-emitting electrochemical cell (PLEC) based on the stretchable AgNW-PDMS electrode and buckling concept, thereby realizing highly stretchable PLECs with excellent performance and mechanical robustness. The luminance intensity of the strained device was optimized to 58 cd m-2 at 7 V under 10% linear strain without damaging the electroluminescence properties. Notably, this effective and practical transfer method provides a way to develop electronic nanowire devices with unique configurations and high performances.