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55 result(s) for "St-Pierre, Yves"
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Towards a Better Understanding of the Relationships between Galectin-7, p53 and MMP-9 during Cancer Progression
It has been almost 25 years since the discovery of galectin-7. This member of the galectin family has attracted interest from many working in the cancer field given its highly restricted expression profile in epithelial cells and the fact that cancers of epithelial origin (carcinoma) are among the most frequent and deadly cancer subtypes. Initially described as a p53-induced gene and associated with apoptosis, galectin-7 is now recognized as having a protumorigenic role in many cancer types. Several studies have indeed shown that galectin-7 is associated with aggressive behavior of cancer cells and induces expression of MMP-9, a member of the matrix metalloproteinases (MMP) family known to confer invasive behavior to cancer cells. It is therefore not surprising that many studies have examined its relationships with p53 and MMP-9. However, the relationships between galectin-7 and p53 and MMP-9 are not always clear. This is largely because p53 is often mutated in cancer cells and such mutations drastically change its functions and, consequently, its association with galectin-7. In this review, we discuss the functional relationships between galectin-7, p53 and MMP-9 and reconcile some apparently contradictory observations. A better understanding of these relationships will help to develop a working hypothesis and model that will provide the basis for further research in the hope of establishing a new paradigm for tackling the role of galectin-7 in cancer.
Targeting intracellular galectins for cancer treatment
Although considerable attention has been paid to the role of extracellular galectins in modulating, positively or negatively, tumor growth and metastasis, we have witnessed a growing interest in the role of intracellular galectins in response to their environment. This is not surprising as many galectins preferentially exist in cytosolic and nuclear compartments, which is consistent with the fact that they are exported outside the cells via a yet undefined non-classical mechanism. This review summarizes our most recent knowledge of their intracellular functions in cancer cells and provides some directions for future strategies to inhibit their role in cancer progression.
Divergent bacterial landscapes: unraveling geographically driven microbiomes in Atlantic cod
Establishing microbiome signatures is now recognized as a critical step toward identifying genetic and environmental factors shaping animal-associated microbiomes and informing the health status of a given host. In the present work, we prospectively collected 63 blood samples of the Atlantic cod population of the Southern Gulf of Saint Lawrence (GSL) and characterized their 16S rRNA circulating microbiome signature. Our results revealed that the blood microbiome signature was dominated at the phylum level by Proteobacteria , Bacteroidetes , Acidobacteria and Actinobacteria , a typical signature for fish populations inhabiting the GSL and other marine ecosystems. At the genus level, however, we identified two distinct cod groups. While the microbiome signature of the first group was dominated by Pseudoalteromonas , a genus we previously found in the microbiome signature of Greenland and Atlantic halibut populations of the GSL, the second group had a microbiome signature dominated by Nitrobacter and Sediminibacterium (approximately 75% of the circulating microbiome). Cods harboring a Nitrobacter/Sediminibacterium -rich microbiome signature were localized in the most southern part of the GSL, just along the northern coast of Cape Breton Island. Atlantic cod microbiome signatures did not correlate with the weight, length, relative condition, depth, temperature, sex, and salinity, as previously observed in the halibut populations. Our study provides, for the first time, a unique snapshot of the circulating microbiome signature of Atlantic cod populations and the potential existence of dysbiotic signatures associated with the geographical distribution of the population, probably linked with the presence of nitrite in the environment.
Comprehensive pathogen diagnostics in wild fish populations using blood-based molecular strategies: an Atlantic herring case study
Climate change affects marine ecosystems by promoting pathogens that threaten key fish populations. To protect these, monitoring programs must adapt to manage threats and sustain fisheries. Here, we combined traditional PCR methods and transcriptomic analysis from a single drop of blood stored on FTA cards to determine the prevalence of erythrocytic necrosis virus (ENV) and the Ichthyophonus parasite in the Atlantic herring population. Across 2023–2024, 33% of individual blood samples tested positive for ENV and 10% for Ichthyophonus by PCR, with ENV-positive fish more frequently found in estuarine and coastal areas. Spatial analyses revealed a clustered distribution for ENV and a more sporadic occurrence of Ichthyophonus . RNA-Seq detected viral RNA fragments in ENV PCR-positive fish, revealing high levels of viral transcripts consistent with active viral replication. However, no significant changes were observed in the host blood transcriptome between infected and uninfected individuals, suggesting that ENV replication may proceed with limited systemic host transcriptional response under subclinical conditions. Overall, our study provides the first comprehensive baseline on the prevalence and molecular activity of ENV and Ichthyophonus in Atlantic herring, demonstrating the power of FTA-based RNA-Seq diagnostics to uncover hidden infections and informing future surveillance and management of wild fish populations.
Insights into the circulating microbiome of Atlantic and Greenland halibut populations: the role of species-specific and environmental factors
Establishing long-term microbiome-based monitoring programs is critical for managing and conserving wild fish populations in response to climate change. In most cases, these studies have been conducted on gut and, to a lesser extent, skin (mucus) microbiomes. Here, we exploited the concept of liquid biopsy to study the circulating bacterial microbiome of two Northern halibut species of economic and ecological importance. Amplification and sequencing of the 16S rRNA gene were achieved using a single drop of blood fixed on FTA cards to identify the core blood microbiome of Atlantic and Greenland halibut populations inhabiting the Gulf of St. Lawrence, Canada. We provide evidence that the circulating microbiome DNA (cmDNA) is driven by genetic and environmental factors. More specifically, we found that the circulating microbiome signatures are species-specific and vary according to sex, size, temperature, condition factor, and geographical localization. Overall, our study provides a novel approach for detecting dysbiosis signatures and the risk of disease in wild fish populations for fisheries management, most notably in the context of climate change.
Intracellular galectin-7 expression in cancer cells results from an autocrine transcriptional mechanism and endocytosis of extracellular galectin-7
The β-galactoside binding protein galectin-7 (gal-7) is constitutively expressed at abnormally high levels in the outside milieu and intracellular compartments of many types of epithelial cancer cells, most notably in aggressive forms of ovarian and breast cancer. It is thus of utmost importance to understand how gal-7 traffics between both intracellular and extracellular compartments to develop novel drugs that target the protumorigenic functions of galectin-7. In the present work, we report that extracellular gal-7 plays a central role in controlling intracellular gal-7 in cells. It does so via two distinct yet complementary mechanisms: firstly by increasing the transcriptional activation of lgals7 gene transcription, and secondly via re-entry into the cells. Increased mRNA levels were dose- and time-dependent and occur in all cell lines tested, including ovarian and breast cancer cell lines. Addition of recombinant gal-7 to MDA-MB-231 transfected with a luciferase reporter vector containing response elements of the lgals7 promoter indicated that increased mRNA level of lgals7 occurs via de novo gene transcription. Re-entry of extracellular gal-7 inside cells was rapid, and reached cytosolic and mitochondrial compartments. Taken together, these findings reveal the existence of a positive self-amplification pathway that regulates intracellular gal-7 expression in breast and ovarian cancer cells.
Species- and site-specific circulating bacterial DNA in Subantarctic sentinel mussels Aulacomya atra and Mytilus platensis
Impacts of climate changes are particularly severe in polar regions where warmer temperatures and reductions in sea-ice covers threaten the ecological integrity of marine coastal ecosystems. Because of their wide distribution and their ecological importance, mussels are currently used as sentinel organisms in monitoring programs of coastal ecosystems around the world. In the present study, we exploited the concept of liquid biopsy combined to a logistically friendly sampling method to study the hemolymphatic bacterial microbiome in two mussel species ( Aulacomya atra and Mytilus platensis ) in Kerguelen Islands, a remote Subantarctic volcanic archipelago. We found that the circulating microbiome signatures of both species differ significantly even though their share the same mussel beds. We also found that the microbiome differs significantly between sampling sites, often correlating with the particularity of the ecosystem. Predictive models also revealed that both species have distinct functional microbiota, and that the circulating microbiome of Aulacomya atra was more sensitive to changes induced by acute thermal stress when compared to Mytilus platensis. Taken together, our study suggests that defining circulating microbiome is a useful tool to assess the health status of marine ecosystems and to better understand the interactions between the sentinel species and their habitat.
Liquid biopsies for omics-based analysis in sentinel mussels
Liquid biopsy of plasma is a simple and non-invasive technology that holds great promise in biomedical research. It is based on the analysis of nucleic acid-based biomarkers with predictive potential. In the present work, we have combined this concept with the FTA technology for sentinel mussels. We found that hemocytes collected from liquid biopsies can be readily fixed on FTA cards and used for long-term transcriptome analysis. We also showed that liquid biopsy is easily adaptable for metagenomic analysis of bacterial profiles of mussels. We finally provide evidence that liquid biopsies contained circulating cell-free DNA (ccfDNA) which can be used as an easily accessible genomic reservoir. Sampling of FTA-fixed circulating nucleic acids is stable at room temperature and does not necessitate a cold-chain protection. It showed comparable performance to frozen samples and is ideally adapted for sampling in remote areas, most notably in polar regions threatened by anthropogenic activities. From an ethical point of view, this minimally-invasive and non-lethal approach further reduces incidental mortality associated with conventional tissue sampling. This liquid biopsy-based approach should thus facilitate biobanking activities and development of omics-based biomarkers in mussels to assess the quality of aquatic ecosystems.
Galectin-7 Expression Potentiates HER-2-Positive Phenotype in Breast Cancer
HER-2 positive tumors are among the most aggressive subtypes of breast cancer and are frequently associated with metastasis and poor outcome. As with other aggressive subtypes of breast cancer, these tumors are associated with abnormally high expression of galectin-7 (gal-7), which confers metastatic breast tumor cells with increased invasive behavior. Although previous studies in the rat model of breast tumorigenesis have shown that gal-7 is also increased in primary breast tumor, its contribution to the development of the primary breast tumors remains unclear. In the present work, we have used genetically-engineered gal-7-deficient mice to examine the role of gal-7 in the development of the mammary gland and of breast cancer. Using histological and immunohistological analysis of whole mammary glands at different stages of development, we detected no significant changes between normal and gal-7-deficient mice. To test the involvement of gal-7 in breast cancer, we next examined the effects of loss of gal-7 on mammary tumor development by crossing gal-7-deficient mice with the mammary tumor transgenic mouse strain FVB-Tg(MMTV-Erbb2)NK1Mul/J. Finally, assessment of mice survival and tumor volume showed a delay of mammary tumor growth in the absence of systemic gal-7. These data suggest that gal-7 could potentiate the phenotype of HER-2 positive primary breast cancer.