Stromal Hedgehog signalling is downregulated in colon cancer and its restoration restrains tumour growth

A role for Hedgehog (Hh) signalling in the development of colorectal cancer (CRC) has been proposed. In CRC and other solid tumours, Hh ligands are upregulated; however, a specific Hh antagonist provided no benefit in a clinical trial. Here we use Hh reporter mice to show that downstream Hh activity is unexpectedly diminished in a mouse model of colitis-associated colon cancer, and that downstream Hh signalling is restricted to the stroma. Functionally, stroma-specific Hh activation in mice markedly reduces the tumour load and blocks progression of advanced neoplasms, partly via the modulation of BMP signalling and restriction of the colonic stem cell signature. By contrast, attenuated Hh signalling accelerates colonic tumourigenesis. In human CRC, downstream Hh activity is similarly reduced and canonical Hh signalling remains predominantly paracrine. Our results suggest that diminished downstream Hh signalling enhances CRC development, and that stromal Hh activation can act as a colonic tumour suppressor

Signals in the Soil: An Introduction to Wireless Underground Communications

In this chapter, wireless underground (UG) communications are introduced. A detailed overview of WUC is given. A comprehensive review of research challenges in WUC is presented. The evolution of underground wireless is also discussed. Moreover, different component of UG communications is wireless. The WUC system architecture is explained with a detailed discussion of the anatomy of an underground mote. The examples of UG wireless communication systems are explored. Furthermore, the differences of UG wireless and over-the-air wireless are debated. Different types of wireless underground channel (e.g., In-Soil, Soil-to-Air, and Air-to-Soil) are reported as well

Characterization of the progressive skin disease and inflammatory cell infiltrate in mice with inhibited NF-kappaB signaling.

A growth inhibitory role in skin development for the NF-kappaB proteins has been established in recent years. We have previously shown that inhibition of NF-kappaB by overexpression of degradation-resistant IkappaB-alpha in the skin results in the development of squamous cell carcinomas (SCC). In this paper, we characterize the progressive skin disease leading to cancer development in mice with inhibited NF-kappaB signaling in the skin. Increased proliferation and a strong inflammatory response were evident in transgenic skin. A mixed inflammatory cell infiltrate dominated by polymorphonuclear leukocytes was observed in concurrence with an upregulation of the proinflammatory cytokine tumor necrosis factor-alpha. This genetically engineered mouse mutation may be a useful tool to test the efficacy of cytokine therapies for SCC in the future

Regulation of Gli1 transcriptional activity in the nucleus by Dyrk1

To investigate the cellular role of dual specificity Yak1-related kinase (Dyrk) 1, a nuclear localized dual specificity protein kinase, we examined its effect on transcriptional regulation using reporter gene assays. We found that Dyrk1 can substantially enhance Gli1-dependent, but not LEF-1-, c-Jun-, or Elk-dependent, gene transcription. In part, Dyrk1 does this through retaining Gli1 in the nucleus. However, we also demonstrate that Dyrk1 can enhance the transcriptional activity of Gli1-AHA, a nuclear export mutant, suggesting that Dyrk1 may be more directly involved in regulating the transcriptional activity of Gli1. In addition, Dyrk1 acted synergistically with Sonic hedgehog (Shh) to induce gene transcription and differentiation in mouse C3H10T1/2 cells. The failure of Shh to stimulate Dyrk1 kinase activity suggests that Dyrk1 may not be directly regulated by the Shh signaling pathway but functionally interacts with it. Thus, Gli1 transcriptional activity may be subjected to further regulation in the cell nucleus by a pathway distinct from Shh signaling, one mediated by Dyrk1.This work was supported by grants from the National Institutes of Health and American Cancer Society and by American Heart Association Established Investigator Award (to D.W.).Peer reviewe