Multiple oestradiol functions inhibit ferroptosis and acute kidney injury.

Acute tubular necrosis mediates acute kidney injury (AKI) and nephron loss, the hallmark of end-stage renal disease. For decades, it has been known that female kidneys are less sensitive to AKI. Acute tubular necrosis involves dynamic cell death propagation by ferroptosis along the tubular compartment.

Polyamines buffer labile iron to suppress ferroptosis.

Polyamines are essential and evolutionarily conserved metabolites present at millimolar concentrations in mammalian cells. Cells tightly regulate polyamine homeostasis through complex feedback mechanisms, yet the precise role necessitating this regulation remains unclear. Here, we show that polyamines function as endogenous buffers of redox-active iron, providing a molecular link between polyamine metabolism and ferroptosis.

Medical management of pancreatic cancer: from personalization to broadening treatment strategies.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most heterogeneous and deadly cancers. This review examines recently implemented strategies to integrate predictive tools and targeted therapies to improve treatments personalization and patient outcomes. Predictive transcriptomic signatures based on machine learning should optimize first-line chemotherapy selection, while organoid-based chemo-profiling could help late-line or non-standard treatments, particularly when transcriptomic signatures are unavailable to guide therapeutic decisions.

Targeting transcription-replication conflicts using G-quadruplexes stabilizers in multiple myeloma.

Replication stress exerts an important role in fueling genomic instability characterizing multiple myeloma (MM) evolution and is a leading cause of drug resistance. Normal and malignant plasma cells (PCs) are associated with a high transcriptional stress due to the huge production of immunoglobulins. Transcription-replication conflicts (TRCs), arising from collisions between replication and transcription machineries, can promote tumor progression and represent an Achilles' heel to cancer cells.

Activation of lysosomal iron triggers ferroptosis in cancer.

Iron catalyses the oxidation of lipids in biological membranes and promotes a form of cell death called ferroptosis. Defining where this chemistry occurs in the cell can inform the design of drugs capable of inducing or inhibiting ferroptosis in various disease-relevant settings. Genetic approaches have revealed suppressors of ferroptosis; by contrast, small molecules can provide spatiotemporal control of the chemistry at work.

Oncogenic and teratogenic effects of , an inflammation-prone mouse model of the human hotspot mutant .

Missense 'hotspot' mutations localized in six p53 codons account for 20% of mutations in human cancers. Hotspot p53 mutants have lost the tumor suppressive functions of the wildtype protein, but whether and how they may gain additional functions promoting tumorigenesis remain controversial. Here, we generated , a mouse model of the human hotspot mutant .

PSL Chemical Biology Symposia: The Increasing Impact of Chemistry in Life Sciences.

This symposium is the 6th Paris Sciences & Lettres (PSL) Chemical Biology meeting (2015, 2016, 2019, 2023, 2024, 2025) being held at Institut Curie. This initiative originally started in 2013 at Institut de Chimie des Substances Naturelles (ICSN) in Gif-sur-Yvette and was mostly focused on organic synthesis. It was then exported at Institut Curie to cover a larger scope, before becoming the official French Chemical Biology meeting.

Ironomycin induces mantle cell lymphoma cell death by targeting iron metabolism addiction.

Mantle-cell lymphoma (MCL) remains an aggressive and incurable cancer. Accumulating evidence reveals that abnormal iron metabolism plays an important role in tumorigenesis and in cancer progression of many tumors. Based on these data, we searched to identify alterations of iron homeostasis in MCL that could be exploited to develop novel therapeutic strategies.

Inhibition of the STAT3/Fanconi anemia axis is synthetic lethal with PARP inhibition in breast cancer.

The targeting of cancer stem cells (CSCs) has proven to be an effective approach for limiting tumor progression, thus necessitating the identification of new drugs with anti-CSC activity. Through a high-throughput drug repositioning screen, we identify the antibiotic Nifuroxazide (NIF) as a potent anti-CSC compound. Utilizing a click chemistry strategy, we demonstrate that NIF is a prodrug that is specifically bioactivated in breast CSCs.

Metal Ion Signaling in Biomedicine.

Complex multicellular organisms are composed of distinct tissues involving specialized cells that can perform specific functions, making such life forms possible. Species are defined by their genomes, and differences between individuals within a given species directly result from variations in their genetic codes. While genetic alterations can give rise to disease-causing acquisitions of distinct cell identities, it is now well-established that biochemical imbalances within a cell can also lead to cellular dysfunction and diseases.

Activation of lysosomal iron triggers ferroptosis in cancer.

Iron catalyses the oxidation of lipids in biological membranes and promotes a form of cell death referred to as ferroptosis. Identifying where this chemistry takes place in the cell can inform the design of drugs capable of inducing or inhibiting ferroptosis in various disease-relevant settings. Whereas genetic approaches have revealed underlying mechanisms of lipid peroxide detoxification, small molecules can provide unparalleled spatiotemporal control of the chemistry at work.

Ether lipids influence cancer cell fate by modulating iron uptake.

Cancer cell fate has been widely ascribed to mutational changes within protein-coding genes associated with tumor suppressors and oncogenes. In contrast, the mechanisms through which the biophysical properties of membrane lipids influence cancer cell survival, dedifferentiation and metastasis have received little scrutiny. Here, we report that cancer cells endowed with a high metastatic ability and cancer stem cell-like traits employ ether lipids to maintain low membrane tension and high membrane fluidity.

PSL Chemical Biology Symposia: Recent Progress in Ferroptosis.

This symposium is the 5th PSL (Paris Sciences & Lettres) Chemical Biology meeting (2015, 2016, 2019, 2023, 2024) held at Institut Curie. This initiative originally started at Institut de Chimie des Substances Naturelles (ICSN) in Gif-sur-Yvette, with a strong focus on chemistry. It was then continued at the Institut Curie (2015) covering a larger scope, before becoming the official PSL Chemical Biology meeting.

Cooperative pro-tumorigenic adaptation to oncogenic RAS through epithelial-to-mesenchymal plasticity.

In breast cancers, aberrant activation of the RAS/MAPK pathway is strongly associated with mesenchymal features and stemness traits, suggesting an interplay between this mitogenic signaling pathway and epithelial-to-mesenchymal plasticity (EMP). By using inducible models of human mammary epithelial cells, we demonstrate herein that the oncogenic activation of RAS promotes ZEB1-dependent EMP, which is necessary for malignant transformation. Notably, EMP is triggered by the secretion of pro-inflammatory cytokines from neighboring RAS-activated senescent cells, with a prominent role for IL-6 and IL-1α.

The chemistry of next-generation sequencing.

The first large genome fully sequenced by next-generation sequencing (NGS) was that of a bacteriophage using sequencing by synthesis (SBS) as a paradigm. SBS in NGS is underpinned by 'reversible-terminator chemistry'. To grow from proof of concept to being both affordable and practical, SBS needed to overcome a series of challenges, each of which required the invention of new chemistries.

Protocol to expand and CRISPR-Cas9 genomic edit murine MAIT cells for subsequent in vivo studies.

Generating knockout mice for target molecules in specific T cell populations, without subset-specific promoters, is time-consuming and costly. Here, we describe steps for enriching mucosal-associated invariant T cells from the thymus, expanding them in vitro and performing a CRISPR-Cas9 knockout. We then detail procedure for injecting the knockout cells into wounded Cd3ε mice and characterizing them in the skin.