IL-6 Stabilizes Twist and Enhances Tumor Cell Motility in Head and Neck Cancer Cells through Activation of Casein Kinase 2

BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN) is the seventh most common cancer worldwide. Unfortunately, the survival of patients with SCCHN has not improved in the last 40 years, and thus new targets for therapy are needed. Recently, elevations in serum level of interleukin 6 (IL-6) and expression of Twist in tumor samples were found to be associated with poor clinical outcomes in multiple types of cancer, including SCCHN. Although Twist has been proposed as a master regulator of epithelial-mesenchymal transition and metastasis in cancers, the mechanisms by which Twist levels are regulated post-translationally are not completely understood. Tumor progression is characterized by the involvement of cytokines and growth factors and Twist induction has been connected with a number of these signaling pathways including IL-6. Since many of the effects of IL-6 are mediated through activation of protein phosphorylation cascades, this implies that Twist expression must be under a tight control at the post-translational level in order to respond in a timely manner to external stimuli. METHODOLOGY/PRINCIPAL FINDINGS: Our data show that IL-6 increases Twist expression via a transcription-independent mechanism in many SCCHN cell lines. Further investigation revealed that IL-6 stabilizes Twist in SCCHN cell lines through casein kinase 2 (CK2) phosphorylation of Twist residues S18 and S20, and that this phosphorylation inhibits degradation of Twist. Twist phosphorylation not only increases its stability but also enhances cell motility. Thus, post-translational modulation of Twist contributes to its tumor-promoting properties. CONCLUSIONS/SIGNIFICANCE: Our study shows Twist expression can be regulated at the post-translational level through phosphorylation by CK2, which increases Twist stability in response to IL-6 stimulation. Our findings not only provide novel mechanistic insights into post-translational regulation of Twist but also suggest that CK2 may be a viable therapeutic target in SCCHN

Communicative ecologies and the value of MyFireWatch to the community of Kununurra

This paper is the culmination of a research project involving four fieldtrips to the remote northwestern Australia town of Kununurra. The primary purpose of the research was to engage Kununurra’s visitors and residents in a participatory methodology for scenario based design to create a community-focused version of a professional fire mapping service, FireWatch. The research resulted in the development of MyFireWatch, a map based website which shows fire hotspots derived from satellite images across Australia, bringing this critical information to non-specialist users. The review of the take-up of MyFireWatch was conducted some 13 months after its launch in Kununurra, and the twelve interviewees involved were very positive overall. Their major concern was that visitors to Kununurra – especially backpackers and the senior self-drive tourists that Australians call ‘grey nomads’ – might not know about the service. A review of the tourist-focused sites in Kununurra reveals that organisations that promote tourism are reluctant to inform tourists about the potential dangers of their holiday destination. Thus, the culture and communication practices of tourism organisations are demonstrated to undermine the usefulness of otherwise valuable technological advances

Role of social belongingness during the post-disaster recovery

The 2030 Agenda for Sustainable Development has established a prime goal of eradicating all kinds of poverty, including extreme poverty which remains as a global challenge and a vital requisite for sustainable development. Out of the 17 Sustainable Development Goals (SDGs) a strong emphasis and key imperative is evolved around the first goal “No Poverty.” Although a significant achievement has been made in achieving the SDGs, we often witness that extreme weather events and associated disasters deplete the hard gains of development

NF-κB in cancer therapy

The transcription factor nuclear factor kappa B (NF-κB) has attracted increasing attention in the field of cancer research from last few decades. Aberrant activation of this transcription factor is frequently encountered in a variety of solid tumors and hematological malignancies. NF-κB family members and their regulated genes have been linked to malignant transformation, tumor cell proliferation, survival, angiogenesis, invasion/metastasis, and therapeutic resistance. In this review, we highlight the diverse molecular mechanism(s) by which the NF-κB pathway is constitutively activated in different types of human cancers, and the potential role of various oncogenic genes regulated by this transcription factor in cancer development and progression. Additionally, various pharmacological approaches employed to target the deregulated NF-κB signaling pathway, and their possible therapeutic potential in cancer therapy is also discussed briefly