NALCN ‐mediated sodium influx confers metastatic prostate cancer cell invasiveness

International audienceThere is growing evidence that ion channels are critically involved in cancer cell invasiveness and metastasis. However, the molecular mechanisms of ion signaling promoting cancer behavior are poorly understood and the complexity of the underlying remodeling during metastasis remains to be explored. Here, using a variety of in vitro and in vivo techniques, we show that metastatic prostate cancer cells acquire a specific Na+ /Ca2+ signature required for persistent invasion. We identify the Na+ leak channel, NALCN, which is overexpressed in metastatic prostate cancer, as a major initiator and regulator of Ca2+ oscillations required for invadopodia formation. Indeed, NALCN-mediated Na+ influx into cancer cells maintains intracellular Ca2+ oscillations via a specific chain of ion transport proteins including plasmalemmal and mitochondrial Na+ /Ca2+ exchangers, SERCA and store-operated channels. This signaling cascade promotes activity of the NACLN-colocalized proto-oncogene Src kinase, actin remodeling and secretion of proteolytic enzymes, thus increasing cancer cell invasive potential and metastatic lesions in vivo. Overall, our findings provide new insights into an ion signaling pathway specific for metastatic cells where NALCN acts as persistent invasion controller

BioacPepFinder: a pipeline for prediction of proteolysis-generated bioactive peptides usable for all protein sources.

International audienc

Involvement of the NLRC5 / MHC class I axis in human colorectal cancer immune surveillance

International audienceMost of patients with colorectal cancer (CRC) without microsatellite instability fail torespond to immune checkpoint blockade (ICB) through poorly understood changes in thetumor microenvironment. Recently, we provided evidence that the tonus of tumor infiltratingT lymphocytes (TILs) is associated to the intra-tumoral activity of Caspase-1 (doi:10.3390/cancers13020189). Bulk RNA-seq analysis of CRC revealed a greater expression level of NLRfamily CARD domain containing 5 (NLRC5) in tumors with a detectable Caspase-1 activity.Given that NLRC5 is a regulator of major histocompatibility complex class I (MHC-I) antigenpresentation, we postulated that NLRC5 may modulate cancer immune surveillance andresponsiveness to ICB. We thereby evaluated the significance of the intratumoral changesin NLRC5 expression in several cohorts of patients. We show that NLRC5 is a favorableprognostic factor of overall survival in 100 CRC and of responsiveness to ICB in 45 metastaticCRC. In agreement, NLRC5 expression in KRAS wild type CRC is of better prognosis andpositively correlates with PD1/PD-L1 axis. Conversely, a negative correlation is observedbetween PRMT5, an epigenetic modifier that represses NLRC5 expression, and PD-1/PD-L1axis. Finally, functional studies using co-cultures of TILs isolated from CRC fragments andcolonic cancer cell lines show that enforced expression of NLRC5 in tumor cells enhancesthe cytotoxic activity of CD8+ TILs (cytokine production, degranulation), via a MHC-I-dependent mechanism. Overall, our findings suggest that NLRC5 could be a valuablebiomarker in CRC and that increasing the NLRC5/MHC-I axis in tumor cells could enhanceanti-tumor immunity and immunotherapeutic responses

Widening exposome exploration by means of complementary HRMS analytical platforms: use case on pesticide exposure

International audienceHuman exposure to food and environmental contaminants (such as pesticides) is generally estimated by indirect methods. Targeted bio-monitoring is a way to assess the internal exposure on a limited number of substances, needing large sample amounts for analyses as rigorous and sensitive as possible. Thus, the human health risks associated with multi-exposure to complex mixtures currently remain under-explored.In this context, the SCREENPEST project aims at providing a unified methodology for large-scale characterisation of human internal exposure to pesticides, via a "suspect profiling" approach, using urine

Dépôts cultuels de pièces d'harnachement de chevaux et éléments de char à Blicquy "Ville d'Anderlecht" durant l'âge du Fer

International audienceThe excavations of the Gallo-Roman sanctuary of Blicquy " Ville d'Anderlecht " (Belgium) brought to light various deposits of metal material dating back to the Late Iron Age. Those deposits of religious nature revealed several assemblages of military equipment (swords with scabbards, spearheads, axes) associated with horse harness parts and chariot elements (wheels tyres, naves bands, eyebolts, phalerae, horse bits...). This paper offers a complete study of the material related to the equestrian world and emphasizes the link with the coastal populations of the British Isles through the presentation of a "vase-heades linch-pin" of exclusively insular manufacture

De Parthénos à Mèter : considérations archéologiques sur les fonctions d'Athéna dans le champ des maternités

International audienceDans la religion grecque antique Athéna est, au même titre qu’Artémis et Hestia, la déesse vierge par excellence. Conçue en dehors de toute matrice féminine, née du crâne de Zeus, Athéna s’inscrit en marge du schéma reproductif habituel. En outre, la déesse échappe au destin traditionnel de la femme dans les sociétés anciennes en refusant le mariage et, de fait, la « douloureuse obligation de la maternité » . Athéna apparaît ainsi comme une figure « déviante » en tant que déesse sans mère, fille de Zeus et éternelle parthenos (vierge), écartée de facto de toute fonction maternelle. Toutefois, si elle est biologiquement inapte à être mère, Athéna joue un rôle dans l’éducation de certains individus ; c’est une déesse kourotrophe (kourotrophos), soit une divinité qui accompagne les jeunes gens du berceau jusqu’à l’âge adulte et préside à certains rites de passages. leMèter), tandis qu’à Athènes elle est la « mère » (matèr) de tous les Athéniens. La déesse est également associée à d’autres puissances divines qui interviennent lors de la grossesse, l’accouchement et/ou la petite enfance. Par conséquent, Athéna agit, à sa manière, dans le champ de la maternité.L’objectif de cette communication est de mettre en évidence l’ambiguïté de la figure d’Athéna en tant que figure maternelle et maternante à travers un ensemble de réflexions sur la maternité des déesses grecques. Il s’agit, surtout, de comprendre quelles sont les capacités d’actions d’Athéna dans le champ des maternités, qu’elles soient réelles et symboliques.Le corpus permettant d’envisager Athéna au prisme de la maternité est réduit. Pour cette raison, nous travaillerons sur l’ensemble du monde grec du VIIIe s. av. J.-C. au Ve s. apr. J.-C. Notre perspective sera pluridisciplinaire et prendra en compte une grande variété de sources, qu’elles soient littéraires, épigraphiques, archéologiques et onomastiques.Par l’analyse de cet ensemble, nous souhaitons mettre en évidence le rapport ambivalent d’Athéna vis-à-vis de la maternité : d’une part, en tant que figure en marge de toute capacité reproductive, puisqu’elle est parthenos ; d’autre part, comme divinité avec des compétences qui touchent à la maternité, mais avec des modes d’action qui lui sont propres. De par ses configurations avec d’autres puissances divines, comme Ilithyie liée à l’accouchement, son lien avec le domaine de la maternité est plus net. Pourtant, Athéna agit avant tout sur la protection et l’intégrité du corps civique, plutôt que sur le corps maternel. En tant que kourotrophos, elle protège le devenir de la cité en préservant et en éduquant ses futurs citoyens

Spatially-resolved metabolomic identifies a reprogramming of lipid metabolism and immune surveillance that are caused by colibactin-producing E. coli infection.

International audienc

Towards a Robust Multiply-Accumulate Cell in Photonics using Phase-Change Materials

National audienceIn this paper we propose a novel approach to multiply-accumulate (MAC) operations in photonics. This approach is based on stochastic computing and on the dynamic behavior of phase-change materials (PCMs), leading to the unique characteristic of automatically storing the result in nonvolatile memory. We demonstrate that, even with perfect lookup tables, the standard approach to PCM scalar multiplication is highly susceptible to perturbations as small as 0.1% of the input power, causing repetitive peaks of 600% relative error. In the same operating conditions, the proposed method achieves an average of 7× improvement in precision

Spatial metabolomics reveals a reprogramming of lipid metabolism by bacterial colibactin supporting immunosuppressive microenvironment in right-sided colon cancer

International audienceIntroduction: Intratumoral bacteria contribute to tumor heterogeneity through poorly understood mechanisms. It has been established thatpatients with right-sided colon cancer (RCC) exhibit a worse prognosis and differences in their tumor-associated biofilms and lipid metabolism when compared to left-sided colon cancer. However, it remains unclear whether and how the tumor-associated biofilm may influencethe lipid metabolic reprogramming of the tumor microenvironment.Materials and methods: To uncover the impact of Colibactin-producing by Escherichia coli (CoPEC) tumor-associated microenvironmentand bacterial structure, 16S rRNA gene sequencing, metabolomic profiling in situ (7T-MALDI-FTICR), qPCR (to detect the presence ofColibactin) and RNA-sequencing/RNAscope were applied to RCC tumors. To confirm the human data, mouse and human colon carcinomacells (MC38 and HCT116, respectively) were infected with the CoPEC clinical strain (11G5) or with its mutant strain that does not produceColibactin (11G5∆clbQ). Metabolomic in vitro results were confirmed using SpiderMass. Additionally, data were validated using a CoPECinfection on the MC38 mice graft model.Results: By applying metabolomic profiling in situ, the presence of Colibactin-producing Escherichia coli (CoPEC) was identified to establish a high-glycerophospholipid microenvironment within RCC that bears oncogenic mutations in APC. Using spatial approaches, werevealed that bacterial microniches are poorly infiltrated by IFNγ-producing CD8+ T-cells. Notably, CoPEC infection leads to lipid dropletaccumulation in MC38 and HCT116 cells. Interestingly, the aforementioned alterations in lipid metabolism positively correlated with immunomodulatory factors among which the human regenerating family member 3 alpha gene (REG3A). Herein, we revealed that engraftedtumors into Reg3b-deficient mice resulted in similar metabolic adaptation of the tumor together with a significant reduction in tumor growthafter CoPEC infection. These data are supported by a decrease in Lpcat1 expression, a gene involved in the remodeling of glycerophospholipids, observed only in 11G5-infected WT mice. In this same sense, we detected similar changes in the presence of CoPEC in APCmutant-status RCC patients’ tumors and APC-mutated HT-29 cells.Conclusion: This work clarifies how CoPEC may shape tumor heterogeneity through their influence on lipid metabolism and will allow exploration into the mechanisms of CoPEC-mediated lipid reprogramming on the efficacy of antitumoral therapy

Industrial legacy and hotel pricing: An application of spatial hedonic pricing analysis in Nord-Pas-de-Calais, France.

International audienceAn old industrial region's legacy can be a serious impediment to the development of tourism and other activities by generating negative externalities and disamenities. The aim of this article is to examine whether the cost of this industrial past as valued by tourists is reflected in hotel rates of the Nord-Pas de Calais region, a forerunner of the Industrial Revolution in France. An analysis based on the hedonic price method is undertaken using geolocalized data, to decompose hotel prices into the implicit prices of a set of attributes, both private and public, including the adverse public attributes inherited from the industrial past (brownfield sites, slag heaps, industrial seaports). By comparing the importance of each factor, our analysis provides useful information for public policy and hotel management strategies. In particular, our estimations reveal a significant negative effect of these adverse inherited public attributes on hotel rates for the Nord-Pas-de-Calais, but in the same order of magnitude as the effect of a tourist attraction, suggesting the potential power of public policy and local regeneration initiatives. Furthermore, our results show that hotel managers can obtain valuable information relative to the choice of a location for initial development, their investment strategy, and their communication strategy