Biology subjects

Ammar, N.

Publications and source records attributed to Ammar, N..

3 recordsLinked to original sources

bioRxiv2026

Cancer cachexia overrides sex-specific traits in Drosophila

Cancer cachexia, a metabolic syndrome characterized by pathologic weight loss, dramatically limits therapeutic options and reduces survival. While the mechanisms by which tumors induce wasting of distant organs (particularly muscle and adipose tissues) remain incompletely understood, the influence of biological sex on cachexia progression is even less clear. Here we investigated phenotypic and molecular manifestations of cachexia in both sexes using a model of inducible intestinal tumors in Drosophila. We show that tumor progression leads to the development of severe cachexia both in males and in females manifested by organ atrophies and an inflammatory state. Nevertheless, both phenotypical and molecular cachexic alterations exhibit striking differences between sexes. Transcriptomic analysis show that many genes differentially expressed at high levels in males under normal conditions become downregulated during cachexia, while their expression is upregulated in cachexic females, and reciprocally. Together, sex-specific deregulation in gene expression and metabolic profiles ultimately converge towards a molecular cachexic state that erase or diminish many sex-specific differences otherwise characteristic of healthy males and females. These findings highlight the interplay between oncogenic stress and biological sex in shaping cachexia phenotypes, shedding light on how sex influences the development of cancer cachexia.

developmental biology↗

bioRxiv2026

SPARC mediates tumour-stroma intercellular communication through endosomal regulation of Delta and Notch signalling

Tumour progression relies on reciprocal communication between genetically altered cancer cells and surrounding stromal cells. While the genetic alterations that initiate tumorigenesis have been extensively studied, the dysregulated feedback signalling provided by co-opted stromal cells remains poorly understood. Here, we used a Drosophila cancer model to address this question and identified the matricellular protein SPARC as a mediator of tumour-stroma communication. SPARC is produced by mesenchymal cells and transferred into epithelial tumour cells, where it is internalized through the endocytic pathway. Following uptake, SPARC accumulates in Rab7 positive late endosomes and colocalize with the Notch ligand Delta. SPARC internalization promotes endosomal enlargement and reduces endosome dynamics. Increased SPARC levels in epithelial tumours indirectly attenuate Notch signalling activity through at least altered Delta trafficking. We further identify the N-terminal acidic domain of SPARC as specifically required for its targeting to Delta-associated endosomes. Together, our findings uncover a stromal feedback mechanism by which SPARC modulates Notch signalling through endosomal regulation during tumour development.

developmental biology↗

bioRxiv2025

Immune tracheal intercellular signalling coordinates the muscle injury response in Drosophila

In skeletal muscle, immune and vascular responses are essential for regeneration, yet the cellular and molecular mechanisms that coordinate their activities to restore tissue function remain unclear. Here, using Drosophila, we uncover a multi-organ signaling program that integrates muscle fibers, macrophages, vascular-like tracheal cells, and the extracellular matrix (ECM) to maintain muscle function in response to acute damage. Muscle injury induces rapid macrophage recruitment and secretion of the FGF-like ligand Branchless (Bnl), which activates FGF/FGFR signalling in tracheal cells and promotes their targeted expansion toward damaged muscle. Concomitantly, macrophages deposit ECM components on the damaged muscle, including Collagen IV, forming a localized microenvironment that restricts Bnl ligand diffusion and facilitates directed tracheal remodelling. Genetic disruption of macrophage-derived Bnl or macrophage-mediated ECM deposition abolishes tracheal remodelling and compromises muscle function following injury. Together, these findings reveal a novel immune-vascular communication program in which macrophages coordinate fibroblast growth factor signalling and ECM organization to shape muscle microenvironment and preserve muscle function following acute damage.

developmental biology↗