The role of post-translation regulation of Twist expression in the tumor progression of squamous cell carcinoma of head and neck

Squamous cell carcinoma of head and neck (SCCHN) is the tenth most common cancer in the world. Unfortunately, the survival of patients with SCCHN has not improved in the last 40 years. Therefore new targets for therapy are needed, and to this end we are studying signaling pathways activated by IL-6 which we have found stimulates cell migration and soft agar growth in SCCHN. Our data show that IL-6 increases TWIST expression in a transcription-independent mechanism in many SCCHN cell lines. Further investigation reveals TWIST can be phosphorylated upon IL-6 treatment. By computation prediction (http://scansite.mit.edu/motifscan_seq.phtml ), we found that TWIST has a putative phosphorylation site for casein kinase 2 (CK2) suggesting that this kinase could serve as a link between IL-6 stimulation and Twist stability. To test this hypothesis, we used a CK2 inhibitor and shRNA to CK2 and found that these interventions inhibited IL-6 stimulation of TWIST stability. In addition, mutation of the putative CK2 phosphorylation site (S18/S20A) in TWIST decreased the amount of phospho-ATP incorporated by TWIST in an in vitro kinase assay, and altered TWIST stability. In Boyd chamber migration assay and wound-healing assay, the CK2 inhibitor, DMAT, was found to decrease the motility of IL-6 stimulated SCCHN cells and over expression of either a wild-type or the hyperphosphorylated mimicking mutant S18/20D –Twist rather than the hypo-phosphorylated mimicking mutant S18/20A-Twist can promote SCCHN cell motility.To our knowledge, this is the first report to identify the importance of IL-6 stimulated CK2 phosphorylation of TWIST in SCCHN. As CK2 inhibitors are currently under phase I clinical trials, our findings indicate that CK2 may be a viable therapeutic target in SCCHN. Therefore, further pre-clinical studies of this inhibitor are underway.

Examining the Relationship Between Media Use and Aggression, Sexuality, and Body Image

Objectives: The primary purpose of this research is to understand the media's impact on individual attitudes and behaviors related to aggression, sexuality, and body image. This research is of particular importance because it uses up-to-date data reflecting effects based on the current media environment. Additionally, it includes a racially diverse sample. Methods: A survey of 407 students at a large, public university was conducted. The survey instrument contained general measures related to media consumption, including overall television, video game, and internet use, as well as more specific questions related to particular types of media, such as pornography. For the dependent variables, questions were included that measured both attitudes and behaviors related to aggression, sexuality, and body image. Results: Consistent with predictions, media use impacted both attitudes and behaviors related to aggression, sexuality, and body image. Specifically, overall television consumption led to increased levels of aggression (r=.18, pr=.20, pr=.24, pr=.42, pr=.40, p Conclusions: The media continue to play an important role in the development of attitudes and behaviors. It is warranted, therefore, to continue to investigate what media can cause negative outcomes, as well as to determine how those outcomes vary based on race and gender.

Editorial

What Value Family? Recognizing the Driving Forces of Services for Families