Search

Anoikis acts as a critical barrier to metastasis by inducing cell death upon cancer cell detachment from the extracellular matrix (ECM), thereby preventing tumor cell dissemination to secondary sites. The induction of anoikis requires the lysosomal-mediated downregulation of epidermal growth factor receptors (EGFRs) leading to termination of pro-survival signaling. In this study, we demonstrate that depletion of pre-mRNA splicing factor 4 kinase (PRP4K; also known as PRPF4B) causes dysregulation of EGFR trafficking and anoikis resistance. We also report a novel cytoplasmic localization of PRP4K at the late endosome, and demonstrate both nuclear and cytoplasmic localization in breast, lung and ovarian cancer tissue. Mechanistically, depletion of PRP4K leads to reduced EGFR degradation following cell detachment from the ECM and correlates with increased TrkB, vimentin and Zeb1 expression. As a result, PRP4K loss promotes sustained growth factor signaling and increased cellular resistance to anoikis in vitro and in a novel zebrafish xenotransplantation model of anoikis sensitivity, as well as increased metastasis in a mouse model of ovarian cancer. Thus, PRP4K may serve as a potential biomarker of anoikis sensitivity in ovarian and other epithelial cancers.

During the last few years, conflicts between agriculture and aquaculture have been an important issue in the Bac Lieu province, Mekong Delta, Vietnam. A large area of rice production has been converted to shrimp or shrimp-rice based production systems that require the intake of saline water into fresh water zones that have been used for agriculture. To manage this conflict, the provincial authorities have reviewed land use plans and identified a buffer zone with a mixed land use system of shrimp-rice (rice in the rainy season and shrimp in the dry season when sluices are opened). Under the CPWF (Challenge Program on Water and Food) Project No. 25, role playing games (RPGs) were applied for analyzing the land and water management strategy of farmers in the buffer zone. The RPGs organized in three villages (Phong Thanh, Ninh Thanh Loi and Vinh Loc) indicate that due to much higher revenue earned from shrimp compared with rice, farmers are attempting numerous techniques to prolong the duration of saline water in their fields for shrimp cultivation. This strategy makes the growing of a subsequent rice crop impossible even in the rainy season, thus requiring harmonization of water management at different levels (farm and canal systems). The results from these RPGs also indicate the need for further research on cultivation techniques for the shrimp-rice systems and on participatory methods to achieve better understanding of farmers' decisions. [ABSTRACT FROM AUTHOR]

The effects of ligand binding and receptor phosphorylation on the interaction of progesterone receptor with specific DNA sequences in the uteroglobin gene were studied by nitro‐cellulose filter binding and DNase I footprinting. High affinity sites were mapped upstream from the transcription start and in the first intron. They contained a common TGTTCACT sequence. These sites were occupied with similar affinity by the receptor, either in its free state, or complexed with the hormone or an antagonist (RU486); and also by receptor which had been phosphorylated in vivo in a hormone‐dependent manner. In all cases identical footprints were observed. These experiments led to the following conclusions. The hormone‐dependency of receptor binding to DNA or chromatin is observed in intact cells and in crude cellular extracts but not with purified receptor. Thus in situ, the unliganded receptor probably interacts with some nuclear component(s) which stabilizes it in a ‘non‐activated’ form (non‐chromatin and non‐DNA binding form). When isolated, the receptor may undergo activation, even in the absence of the hormone. Binding by receptor of an antihormone (and possibly receptor phosphorylation) exerts an effect on gene transcription through a mechanism which is different from (and probably follows) receptor interaction with the gene.