ORAI family channels have emerged as important players in malignant transformation, yet the way in which they reprogram cancer cells remains elusive. Here we show that the relative expression levels of ORAI proteins in prostate cancer are different from that in noncancerous tissue. By mimicking ORAI protein remodeling observed in primary tumors, we demonstrate in in vitro models that enhanced ORAI3 expression favors heteromerization with ORAI1 to form a novel channel. These channels support store-independent Ca(2+) entry, thereby promoting cell proliferation and a smaller number of functional homomeric ORAI1-based store-operated channels, which are important in supporting susceptibility to apoptosis. Thus, our findings highlight disrupted dynamic equilibrium of channel-forming proteins as an oncogenic mechanism.

TCAF1 and TCAF2 bind to TRPM8 and promote its cell surface trafficking but differentially regulate its gating properties, leading to opposing effects on prostate cancer cell migration.

The antitumor effects of pharmacologic inhibitors of angiogenesis are hampered in patients by the rapid development of tumor resistance, notably through increased invasiveness and accelerated metastasis. Here, we reevaluated the role of the endogenous antiangiogenic thrombospondin 1 (TSP1) in prostate carcinomas in which angiogenesis is an active process. In xenografted tumors, we observed that TSP1 altogether inhibited angiogenesis and fostered tumor development. Our results show that TSP1 is a potent stimulator of prostate tumor cell migration. This effect required CD36, which also mediates TSP1 antiangiogenic activity, and was mimicked by an antiangiogenic TSP1-derived peptide. As suspected for pharmacologic inhibitors of angiogenesis, the TSP1 capacities to increase hypoxia and to trigger cell migration are thus inherently linked. Importantly, although antiangiogenic TSP1 increases hypoxia in vivo, our data show that, in turn, hypoxia induced TSP1, thus generating a vicious circle in prostate tumors. In radical prostatectomy specimens, we found TSP1 expression significantly associated with invasive tumors and with tumors which eventually recurred. TSP1 may thus help select patients at risk of prostate-specific antigen relapse. Together, the data suggest that intratumor disruption of the hypoxic cycle through TSP1 silencing will limit tumor invasion.

Background Cross-border malaria is a significant obstacle to achieving malaria control and elimination worldwide. Objective This study aimed to build a cross-border surveillance system that can make comparable and qualified data available to all parties involved in malaria control between French Guiana and Brazil. Methods Data reconciliation rules based on expert knowledge were defined and applied to the heterogeneous data provided by the existing malaria surveillance systems of both countries. Visualization dashboards were designed to facilitate progressive data exploration, analysis, and interpretation. Dedicated advanced open source and robust software solutions were chosen to facilitate solution sharing and reuse. Results A database gathering the harmonized data on cross-border malaria epidemiology is updated monthly with new individual malaria cases from both countries. Online dashboards permit a progressive and user-friendly visualization of raw data and epidemiological indicators, in the form of time series, maps, and data quality indexes. The monitoring system was shown to be able to identify changes in time series that are related to control actions, as well as differentiated changes according to space and to population subgroups. Conclusions This cross-border monitoring tool could help produce new scientific evidence on cross-border malaria dynamics, implementing cross-border cooperation for malaria control and elimination, and can be quickly adapted to other cross-border contexts.

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Despite the successes of antiretrovirals, patients presenting with advanced HIV are still common and they are still at risk of dying. Improved diagnosis, and notably systematic screening with appropriate tools are still important areas of potential progress.

Background Due to their genetic characteristics, their isolation in rainforest areas, and their traditional way of life, Amerindian populations are likely to suffer from a specific spectrum of dermatoses. However, there are few available data on such skin disorders. Our aims were to describe all skin disorders in two Amerindian villages of French Guiana. Methods This retrospective study concerned all patients who consulted in the HealthCentres of Camopi and Trois-Sauts between July 1, 2017, and December 31, 2018. We included all patients classified with an ICD code linked to a skin disorder. All medical records were cross-checked by two dermatologists to correct misclassifications.Results A total of 639 patients formed the study population, for 866 different skin disorders. Non-sexually transmitted infections represented 57.6% of all skin disorders, followed by eczema (11.5%) and bites/envenomations (9.1%). Bacteria were responsible for 238 skin infections, followed by fungi (141 cases) and parasites (69 cases, including 43 scabies, nine cutaneous leishmaniasis, and two tungiasis). We reported a low prevalence of sexually transmitted infections (10 cases) and an absence of skin cancers. ConclusionsThis study revealed the absence of skin cancer in the Amerindian population of the Upper Oyapock and the important burden of infectious and animal-related diseases. Future studies should assess a possible underestimation of sexually transmitted diseases in this area. Public health policies should target neglected diseases such as cutaneous leishmaniasis, tungiasis, scabies, and envenomations. Atopic dermatitis was a significant and unexpected cause of consultations. Dermatological conditions in the Amerindian villages of French Guiana have never been described. About 12,000 Amerindians live in this territory, divided into six different ethnic groups. Many of them live in cities where ethnic diversity makes their study difficult, and the selection of patients according to ª

Markers of prostate tumor recurrence after radical prostatectomy are lacking and highly demanded. The androgen receptor (AR) is a nuclear receptor that plays a pivotal role in normal and cancerous prostate tissue. AR interacts with a number of proteins modulating its stability, localization, and activity. To test the hypothesis that an increased expression of AR partners might foster tumor development, we immunopurified AR partners in human tumors xenografted into mice. One of the identified AR partners was the multifunctional enzyme carbamoyl-phosphate synthetase II, aspartate transcarbamylase, and dihydroorotase (CAD), which catalyzes the 3 initial steps of pyrimidine biosynthesis. We combined experiments in C4-2, LNCaP, 22RV1, and PC3 human prostate cell lines and analysis of frozen radical prostatectomy samples to study the CAD-AR interaction. We show here that in prostate tumor cells, CAD fosters AR translocation into the nucleus and stimulates its transcriptional activity. Notably, in radical prostatectomy specimens, CAD expression was not correlated with proliferation markers, but a higher CAD mRNA level was associated with local tumor extension (P=0.049) and cancer relapse (P=0.017). These results demonstrate an unsuspected function for a key metabolic enzyme and identify CAD as a potential predictive marker of cancer relapse.