Géraldine Gentric

• PhD
• PhD at Institut Curie

Although heterogeneity of FAP+ Cancer-Associated Fibroblasts (CAF) has been described in breast cancer, their plasticity and spatial distribution remain poorly understood. Here, we analyze trajectory inference, deconvolute spatial transcriptomics at single-cell level and perform functional assays to generate a high-resolution integrated map of brea...

The Yes-associated protein (YAP) oncoprotein has been linked to both metastases and resistance to targeted therapy of lung cancer cells. We aimed to investigate the effect of YAP pharmacological inhibition, using YAP/TEA domain (TEAD) transcription factor interaction inhibitors in chemo-resistant lung cancer cells. YAP subcellular localization, as...

Although cancer-associated fibroblast (CAF) heterogeneity is well-established, the impact of chemotherapy on CAF populations remains poorly understood. Here we address this question in high-grade serous ovarian cancer (HGSOC), in which we previously identified 4 CAF populations. While the global content in stroma increases in HGSOC after chemothera...

Background: The Yes-associated protein (YAP) oncoprotein has been linked to both metastasis and resistance to targeted therapy of lung cancer cells. We aimed to investigate the effect of YAP pharmacological inhibition, using YAP/ TEA domain (TEAD) transcription factor interaction inhibitors, in chemo-resistant lung cancer cells. Methods: YAP subcel...

Resistance to endocrine treatments and CDK4/6 inhibitors is considered a near-inevitability in most patients with estrogen receptor positive breast cancers (ER + BC). By genomic and metabolomics analyses of patients’ tumours, metastasis-derived patient-derived xenografts (PDX) and isogenic cell lines we demonstrate that a fraction of metastatic ER...

Simple Summary Cancer-associated SF3B1 mutations result in aberrant transcripts whose fate remains unknown. We aimed to investigate the functional consequences of these splice aberrations. Our results show that SF3B1 mutation alters the translation of transcripts encoding proteins involved in metabolism, which triggers a metabolic switch toward an...

Succinate dehydrogenase is a key enzyme in the tricarboxylic acid cycle and the electron transport chain. All four subunits of succinate dehydrogenase are tumor suppressor genes predisposing to paraganglioma, but only mutations in the SDHB subunit are associated with increased risk of metastasis. Here we generated an Sdhd knockout chromaffin cell l...

Simple Summary Tumors are a complex ecosystem including not only cancer cells, but also many distinct cell types of the tumor micro-environment. While the Warburg effect assessing high glucose uptake in tumors was recognized a long time ago, metabolic heterogeneity within tumors has only recently been demonstrated. Indeed, several recent studies ha...

A subset of cancer-associated fibroblasts (FAP⁺/CAF-S1) mediates immunosuppression in breast cancers, but its heterogeneity and its impact on immunotherapy response remain unknown. Here, we identify 8 CAF-S1 clusters by analyzing more than 19,000 single CAF-S1 fibroblasts from breast cancer. We validate the five most abundant clusters by flow cytom...

Objectives Polyploidy is a fascinating characteristic of liver parenchyma. Hepatocyte polyploidy depends on the DNA content of each nucleus (nuclear ploidy) and the number of nuclei per cell (cellular ploidy). Which role can be assigned to polyploidy during human hepatocellular carcinoma (HCC) development is still an open question. Here, we investi...

Table S2. List of Metabolic Proteins Differentially Expressed in High- and Low-OXPHOS HGSOCs, Related to Figure 1 List of proteins differentially expressed in high- and low-OXPHOS HGSOC, derived from Possemato et al. (2011) and analyzed in Figure 1. Proteins are named by uniprot and gene symbols. p values are calculated from Mann-Whitney test, adj...

Table S4. List of All Detected Proteins Detected in High- and Low-OXPHOS HGSOCs from the Curie Cohort, Related to Figure 1

Table S5. List of All Detected Metabolites Detected in High- and Low-OXPHOS HGSOCs from the Curie Cohort, Related to Figure 1

High-grade serous ovarian cancer (HGSOC) remains an unmet medical challenge. Here, we unravel an unanticipated metabolic heterogeneity in HGSOC. By combining proteomic, metabolomic, and bioergenetic analyses, we identify two molecular subgroups, low- and high-OXPHOS. While low-OXPHOS exhibit a glycolytic metabolism, high-OXPHOS HGSOCs rely on oxida...

High-grade serous ovarian cancers (HGSOC) have been subdivided into molecular subtypes. The mesenchymal HGSOC subgroup, defined by stromal-related gene signatures, is invariably associated with poor patient survival. We demonstrate that stroma exerts a key function in mesenchymal HGSOC. We highlight stromal heterogeneity in HGSOC by identifying fou...

Significance: In the last years, metabolic reprogramming, fluctuations in bioenergetic fuels and modulation of oxidative stress became new key hallmarks of tumor development. In cancer, elevated glucose uptake and high glycolytic rate, as source of ATP, constitute a growth advantage for tumors. This represents the universally known "Warburg effect...

Polyploidization is one of the most dramatic changes that can occur in the genome. In the liver, physiological polyploidization events occur during both liver development and throughout adult life. Here, we determined that a pathological polyploidization takes place in nonalcoholic fatty liver disease (NAFLD), a widespread hepatic metabolic disorde...

Polyploidy (alias whole genome amplification) refers to organisms containing more than two basic sets of chromosomes. Polyploidy was first observed in plants more than a century ago, and it is known that such processes occur in many eukaryotes under a variety of circumstances. In mammals, the development of polyploid cells can contribute to tissue...

AMP-activated protein kinase (AMPK) is an evolutionarily conserved sensor of cellular energy status that contributes to restoration of energy homeostasis by slowing down ATP-consuming pathways and activating ATP-producing pathways. Unexpectedly, in different system, AMPK is also required for proper cell division. In the current study, we evaluated...

Most cells in mammalian tissues usually contain a diploid complement of chromosomes. However, numerous studies have demonstrated a major role of "diploid-polyploid conversion" during physiopathological processes in several tissues. In the liver parenchyma, progressive polyploidization of hepatocytes takes place during postnatal growth. Indeed, at t...

Organisms containing an increase in DNA content by whole number multiples of the entire set of chromosomes are defined as polyploid. Cells that contain more than two sets of chromosomes were first observed in plants about a century ago, and it is now recognized that polyploid cells form in many eukaryotes under a wide variety of circumstances. Alth...