Transformed epithelia trigger non-tissue-autonomous tumor suppressor response by adipocytes via activation of toll and Eiger/TNF signaling

High tumor burden is associated with increased levels of circulating inflammatory cytokines that influence the pathophysiology of the tumor and its environment. The cellular and molecular events mediating the organismal response to a growing tumor are poorly understood. Here, we report a bidirectional crosstalk between epithelial tumors and the fat body—a peripheral immune tissue—in Drosophila. Tumors trigger a systemic immune response through activation of Eiger/TNF signaling, which leads to Toll pathway upregulation in adipocytes. Reciprocally, Toll elicits a non-tissue-autonomous program in adipocytes, which drives tumor cell death. Hemocytes play a critical role in this system by producing the ligands Spätzle and Eiger, which are required for Toll activation in the fat body and tumor cell death. Altogether, our results provide a paradigm for a long-range tumor suppression function of adipocytes in Drosophila, which may represent an evolutionarily conserved mechanism in the organismal response to solid tumors

FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells

Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours

A shape memory polymer concrete crack closure system activated by electrical current

YesThe presence of cracks has a negative impact on the durability of concrete by providing paths for corrosive materials to the embedded steel reinforcement. Cracks in concrete can be closed using shape memory polymers (SMP) which produce a compressive stress across the crack faces. This stress has been previously found to enhance the load recovery associated with autogenous selfhealing. This paper details the experiments undertaken to incorporate SMP tendons containing polyethylene terephthalate (PET) filaments into reinforced and unreinforced 500 × 100 × 100 mm structural concrete beam samples. These tendons are activated via an electrical supply using a nickelchrome resistance wire heating system. The set-up, methodology and results of restrained shrinkage stress and crack closure experiments are explained. Crack closure of up to 85% in unreinforced beams and 26%–39% in reinforced beams is measured using crack-mouth opening displacement, microscope and digital image correlation equipment. Conclusions are made as to the effectiveness of the system and its potential for application within industry.EPSRC for their funding of the Materials for Life (M4L) project (EP/K026631/1) and Costain Group PLC for industrial sponsorship of the project and autho