BackgroundTreatment of breast cancer patients with distant metastases represents one of the biggest challenges in today’s gynecological oncology. Therefore, a better understanding of mechanisms promoting the development of metastases is of paramount importance. The serine/threonine kinase AKT was shown to drive cancer progression and metastasis. However, there is emerging data that single AKT isoforms (i.e. AKT1, AKT2 and AKT3) have different or even opposing functions in the regulation of cancer cell migration in vitro, giving rise to the hypothesis that inhibition of distinct AKT isoforms might have undesirable effects on cancer dissemination in vivo.MethodsThe triple negative breast cancer cell line MDA-MB-231 was used to investigate the functional roles of AKT in migration and metastasis. AKT single and double knockdown cells were generated using isoform specific shRNAs. Migration was analyzed using live cell imaging, chemotaxis and transwell assays. The metastatic potential of AKT isoform knockdown cells was evaluated in a subcutaneous xenograft mouse model in vivo.ResultsDepletion of AKT3, but not AKT1 or AKT2, resulted in increased migration in vitro. This effect was even more prominent in AKT2,3 double knockdown cells. Furthermore, combined downregulation of AKT2 and AKT3, as well as AKT1 and AKT3 significantly increased metastasis formation in vivo. Screening for promigratory proteins revealed that downregulation of AKT3 increases the expression of S100A4 protein. In accordance, depletion of S100A4 by siRNA approach reverses the increased migration induced by knockdown of AKT3.ConclusionsWe demonstrated that knockdown of AKT3 can increase the metastatic potential of triple negative breast cancer cells. Therefore, our results provide a rationale for the development of AKT isoform specific inhibitors.

Infections of maize with phytopathogenic and toxinogenic Fusarium spp. may occur throughout the cultivation period. This can cause different types of diseases in vegetative and generative organs of the plant. Along with these infections, mycotoxins are often produced and accumulated in affected tissues, which could pose a significant risk on human and animal health when entering the food and feed chain. Most important fungal species infecting European maize belong to the Fusarium sections Discolour and Liseola, the first being more prevalent in cooler and humid climate regions than the second predominating in warmer and dryer areas. Coexistence of several Fusarium spp. pathogens in growing maize under field conditions is the usual case and may lead to multi-contamination with mycotoxins like trichothecenes, zearalenone and fumonisins. The pathways how the fungi gain access to the target organs of the plant are extensively described in relation to specific symptoms of typical rot diseases regarding ears, kernels, rudimentary ears, roots, stem, leaves, seed and seedlings. Both Gibberella and Fusarium ear rots are of major importance in affecting the toxinogenic quality of grain or ear-based products as well as forage maize used for human or animal nutrition. Although rudimentary ears may contain high amounts of Fusarium toxins, the contribution to the contamination of forage maize is minor due to their small proportion on the whole plant dry matter yield. The impact of foliar diseases on forage maize contamination is regarded to be low, as Fusarium infections are restricted to some parts on the leaf sheaths and husks. Mycotoxins produced in rotted basal part of the stem may contribute to forage maize contamination, but usually remain in the stubbles after harvest. As the probability of a more severe disease progression is increasing with a prolonged cultivation period, maize should be harvested at the appropriate maturity stage to keep Fusarium toxin contamination as low as possible. Ongoing surveillance and research is needed to recognise changes in the spectrum of dominating Fusarium pathogens involved in mycotoxin contamination of maize to ensure safety in the food and feed chain.

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