ß-Cyanoalanine synthase protects mites against Arabidopsis defenses.

Glucosinolates are antiherbivory chemical defense compounds in Arabidopsis (Arabidopsis thaliana). Specialist herbivores that feed on brassicaceous plants have evolved various mechanisms aimed at preventing the formation of toxic isothiocyanates. In contrast, generalist herbivores typically detoxify isothiocyanates through glutathione conjugation upon exposure. Here, we examined the response of an extreme generalist herbivore, the two-spotted spider mite Tetranychus urticae (Koch), to indole glucosinolates. Tetranychus urticae is a composite generalist whose individual populations have a restricted host range but have an ability to rapidly adapt to initially unfavorable plant hosts. Through comparative transcriptomic analysis of mite populations that have differential susceptibilities to Arabidopsis defenses, we identified ß-cyanoalanine synthase of T. urticae (TuCAS), which encodes an enzyme with dual cysteine and ß-cyanoalanine synthase activities. We combined Arabidopsis genetics, chemical complementation and mite reverse genetics to show that TuCAS is required for mite adaptation to Arabidopsis through its ß-cyanoalanine synthase activity. Consistent with the ß-cyanoalanine synthase role in detoxification of hydrogen cyanide (HCN), we discovered that upon mite herbivory, Arabidopsis plants release HCN. We further demonstrated that indole glucosinolates are sufficient for cyanide formation. Overall, our study uncovered Arabidopsis defenses that rely on indole glucosinolate-dependent cyanide for protection against mite herbivory. In response, Arabidopsis-adapted mites utilize the ß-cyanoalanine synthase activity of TuCAS to counter cyanide toxicity, highlighting the mite's ability to activate resistant traits that enable this extreme polyphagous herbivore to exploit cyanogenic host plants.

Glycolytic inhibitor 2-Deoxy-d-Glucose activates migration and invasion in glioblastoma cells through modulation of the miR-7-5p/TFF3 signaling pathway.

Glioblastomas (GBMs) are characterized by the metabolic shift towards aerobic glycolysis, rapid proliferation and acquisition of the migratory and invasive phenotype aiding tumor angiogenesis. The glycolytic inhibitor 2-Deoxy-d-glucose (2-DG) used for targeting glycolysis in GBMs is ineffective in inhibiting migration and invasion. In the present study we report that 2-DG treatment downregulates the tumor suppressive miR-7-5p in GBM cell lines in vitro. Overexpression of miR-7-5p significantly reduced migration and invasion in GBM cell lines. The 2-DG induced suppression of miR-7-5p in turn activated the PI3K/Akt signaling activator Trefoil Factor 3 (TFF3) in GBM cell lines. TFF3 was found to be upregulated in cell lines and clinical samples and its genomic inhibition significantly decreased migration and invasion in GBM cell lines either alone or in combination with 2-DG. Collectively, our results provide the molecular basis for the limited efficacy of 2-DG monotherapy and underscores the significance of the miR-7-5p/TFF3 signaling pathway in the regulation of migration and invasion in 2-DG treated GBM cell lines.