Biology subjects

Geminard, C.

Publications and source records attributed to Geminard, C..

6 recordsLinked to original sources

bioRxiv2026

Furan fatty acid supplementation protects against muscle atrophy during cancer cachexia

Background: Cachexia is a multifactorial syndrome frequently observed in cancer patients, characterized by progressive weight loss, muscle atrophy, and systemic inflammation. We recently demonstrated that supplementation with FuFA-F2, a naturally occurring lipid found in various foods, increases muscle mass in different metabolic contexts. Here, we investigated whether FuFA-F2 supplementation could prevent tumor-induced muscle wasting and preserve skeletal muscle integrity during cancer cachexia. Methods: In vitro, C2C12 myotubes were exposed to TNF and IFN{gamma} to mimic cachectic conditions, and the effects of FuFA-F2 on myotube morphology were assessed. In vivo, cancer cachexia was induced by subcutaneous injection of C26 adenocarcinoma cells into male CD2F1 mice. Three groups were compared: non-grafted control mice, untreated C26 tumor-bearing mice, and C26 tumor-bearing mice orally supplemented with FuFA-F2 (13 mg/kg/day) for 14 days. Results: In C2C12 myotubes, TNF and IFN{gamma} exposure reduced myotube area by 17% (p < 0.05), whereas FuFA-F2 treatment prevented this atrophy and restored myotube area to control levels (p < 0.05). In vivo, FuFA-F2 supplementation prevented muscle wasting in C26 tumor-bearing mice without affecting tumor growth or the loss of white adipose tissue. After 14 days, hindlimb muscle weight was reduced by 22% in C26 mice compared with controls (0.706 vs. 0.903 g, p < 0.05), whereas muscle weight in FuFA-F2-treated mice (0.835 g) was not significantly different from controls. Consistently, spontaneous wheel activity was markedly reduced in C26 mice during the final four days (-79%; 3.4 vs. 16.5 km, p < 0.05), whereas FuFA-F2-treated mice maintained activity levels closer to those of controls (11.2 km). RNA-seq analysis revealed extensive transcriptional reprogramming of skeletal muscle in response to C26 tumor growth, with 5,465 differentially expressed genes (DEGs; 32% of detected genes) between Control and C26 mice. Notably, FuFA-F2 substantially attenuated this response, with only 366 DEGs (2%) between Control and C26 + FuFA-F2 mice, and principal component analysis (PCA) showed a transcriptomic profile closer to controls. Tumor-induced alterations involved pathways related to proteostasis, inflammation, and tissue remodeling, which were largely prevented or attenuated by FuFA-F2. Consistent with these findings, FuFA-F2 prevented the induction of Myostatin, Activin A, MAFbx and MuRF1, and attenuated muscle fibrosis and local inflammation. Conclusions: These findings demonstrate that FuFA-F2 preserves skeletal muscle mass and function in the C26 model of cancer cachexia, despite ongoing tumor progression. FuFA-F2 markedly attenuates tumor-induced transcriptional reprogramming and associated catabolic, inflammatory and fibrotic responses, supporting its potential as a therapeutic strategy to preserve skeletal muscle during cancer cachexia.

cancer biology↗

bioRxiv2025

Tumour-derived Ilp8 and Upd3 control intestinal progenitor cells depletion during cachexia in Drosophila larvae

In animals, tumour development triggers systemic effects, impacting the physiology of distant organs. In Drosophila larvae, wing disc neoplastic tumours result in developmental delay and organ wasting reminiscent of cachexia. This paraneoplastic syndrome affects many organs, but its effects on the intestine, a key organ in the regulation of nutrient and energy homeostasis, remain understudied. We describe here that neoplastic tumours also affect the development of the larval midgut, leading to altered cell type numbers, with a depletion of the stem-cell-like Adult Midgut Precursors (AMPs), and a disorganisation of the niche cells which enter precocious differentiation. Importantly, these intestinal cell type alterations are initiated before the onset of reduced food intake, and of muscle and adipose tissue atrophies, and thus represent a new paraneoplastic phenotype. Screening for mediators, we show that tumour derived Ilp8 and Upd3 control AMPs number and niche specification respectively.

developmental biology↗

bioRxiv2023

Fat body glycolysis defects inhibit mTOR and promote distant muscle disorganization through TNF-α/egr and ImpL2 signaling in Drosophila larvae

The fat body in Drosophila larvae serves as a reserve tissue and participates, through its endocrine function, in the regulation of organismal growth and homeostasis. To better understand its role in growth coordination, we induced severe fat body atrophy by knocking down in adipose cells several key enzymes of the glycolytic pathway. Our results show that impairing the last steps of glycolysis led to a drastic shrinkage in adipose cell size and lipid droplets content, and a downregulation of the mTOR pathway. Strikingly, fat body atrophy resulted in the distant disorganization of body wall muscles and the release of muscle-specific proteins in the hemolymph. Molecularly we showed that REPTOR activity was required for fat body atrophy downstream of glycolysis inhibition, and that the effect of fat body atrophy on muscles did not require upd3 secretion, but depended the production of egr/TNF- and of the insulin pathway inhibitor ImpL2.

physiology↗

bioRxiv2020

MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis

Alterations to cell polarization or to intercellular junctions are often associated with epithelial cancer progression, including breast cancers (BCa). We show here that the loss of the junctional scaffold protein MAGI1 is associated with bad prognosis in luminal BCa, and promotes tumorigenesis. E-cadherin and the actin binding scaffold AMOTL2 accumulate in MAGI1 deficient cells which are subjected to increased stiffness. These alterations are associated with low YAP activity, the terminal Hippo-pathway effector, but with an elevated ROCK and p38 Stress Activated Protein Kinase activities. Blocking ROCK prevented p38 activation, suggesting that MAGI1 limits p38 activity in part through releasing actin strength. Importantly, the increased tumorigenicity of MAGI1 deficient cells is rescued in the absence of AMOTL2 or after inhibition of p38, demonstrating that MAGI1 acts as a tumor-suppressor in luminal BCa by inhibiting an AMOTL2/p38 stress pathway.

cancer biology↗

bioRxiv2020

Loss of epithelial polarity redirects Notch signaling and triggers a Xrp1 response during neoplastic growth in Drosophila

Aggressive neoplastic growth can be initiated by a limited number of genetic alterations, such as the well-established cooperation between loss of cell architecture and hyperactive signaling pathways. However, our understanding of how these different alterations interact and influence each other remains very incomplete. Using Drosophila paradigms of imaginal wing disc epithelial growth, we have monitored the changes in Notch pathway activity according to the polarity status of cells (scrib mutant). We show that the scrib mutation impacts the direct transcriptional output of the Notch pathway, without altering the global distribution of Su(H), the Notch dedicated transcription factor. The Notch-dependent neoplasms require however, the action of a group of transcription factors, similar to those previously identified for Ras/scrib neoplasm (namely AP-1, Stat92E, Ftz-F1, and bZIP factors), further suggesting the importance of this transcription factor network during neoplastic growth. Finally our work highlights some Notch/scrib specificities, in particular the role of the PAR domain containing bZIP transcription factor and Notch direct target Pdp1 for neoplastic growth.

developmental biology↗

bioRxiv2018

Myosin1D is an evolutionarily conserved determinant of animal Left/Right asymmetry

The establishment of Left/Right (LR) asymmetry is fundamental to animal development. While the pathways governing antero-posterior and dorso-ventral patterning are well conserved among different phyla, divergent mechanisms have been implicated in the specification of LR asymmetry in vertebrates and invertebrates. A cilia-driven, directional fluid flow is important for symmetry breaking in numerous vertebrates, including zebrafish1-10. Alternatively, LR asymmetry can be established independently of motile cilia, notably through the intrinsic chirality of the acto-myosin cytoskeleton11-18. Here we show that MyosiniD (Myo1D), which has been previously identified as a key determinant of LR asymmetry in Drosophila12,13, is essential for the formation and the function of the zebrafish LR Organizer (LRO). We show that Myo1D controls the polarity of LRO cilia and interacts functionally with the Planar Cell Polarity (PCP) gene VanGogh-like2 (Vangl2)19, to promote the establishment of a functional LRO flow. Our findings identify Myo1D as the first evolutionarily conserved determinant of LR asymmetry, and show that functional interactions between Myo1D and PCP are central to the establishment of animal LR asymmetry.

developmental biology↗