Highlights of This Issue

Abstract

By using human prostate cancer samples in which high-grade prostatic intraepithelial neoplasia (HGPIN) coexists with prostate cancer, and transgenic mouse models that show that dysregulated prostate-specific c-Myc expression leads to mouse PIN and prostate cancer, Yang and colleagues showed a positive association between c-Myc expression and caveolin-1 (Cav-1) upregulation in the context of neoplastic prostatic growth. Additional experiments suggested that a c-Myc-VEGF-Cav-1 positive-feedback cycle underlies this relationship. Overall, the results of this study nominate a clinically relevant molecular model that links HGPIN and prostate cancer and reveal an important role for c-Myc-Cav-1 interactions in prostate carcinogenesis.K-Ras GTPase is mutated in 90% of pancreatic adenocarcinomas and regulates invasive gene pathways. MAPK signaling is activated in patient biopsies, but was hitherto not detected in conventional 2-D cultures of pancreatic cancer cells. Using normal and transformed cell lines and working in 3-D models, Botta and colleagues were able to recapitulate an invasive phenotype concomitant with isoform specific ERK2 activation and MMP-1 overexpression, but only in cells that harbor mutant K-Ras. The ability of small molecule inhibitors or RNAi to inactivate ERK2 or MMP-1 and dampen invasion opens the path to novel specific pancreatic cancer therapeutic targets.Because hypoxia and neuroendocrine differentiation (NED) have been linked to prostate cancer progression, unfavorable outcome, and castration resistance, Danza and coworkers sought to determine whether there was a correlation between low oxygen tension, degree of NED, and androgen independency, in vitro. As a result, for the first time, it has been shown that hypoxia promotes NED and attenuation of androgen receptor expression, which appear to be driven by inhibition of Notch signaling. Modulation of Notch pathway may slow down the progression of prostate cancer toward a neuroendocrine-mediated, androgenindependent phenotype.The nuclear translocation of β-catenin is a common event in the progression of several types of cancers, including cervical cancer. The relationship between the oncogenic mechanisms of HPV and Wnt signaling activation is poorly understood. Using both, cell culture and transgenic mice as study models, Bonilla-Delgado and colleagues show that E6-HPV16 oncoprotein may play a key role in the enhancement of canonical Wnt signaling. At present, the knowledge of cellular mechanisms deregulated during HPVinduced carcinogenesis is the basis for the development of future therapeutic strategies in the treatment of HPV-infected women.