Biology subjects

Casali, A.

Publications and source records attributed to Casali, A..

3 recordsLinked to original sources

bioRxiv2025

Pro-tumoral Ca2+ signaling is dependent on Ca-alpha1T and Slowpoke channels in Drosophila melanogaster glioma

BackgroundIon channel-mediated cytosolic Ca2+ oscillations play a crucial role in promoting the growth of glioblastoma, a tumor of poor prognosis. Here, we have studied the roles of Ca-1T and Slowpoke ion channels in a Drosophila melanogaster glioblastoma model. Although their mammalian orthologs have been implicated in glioblastoma cell viability in vitro, their oncogenic potential remains uncharacterized in a complex in vivo context. ResultsWe show that glial-specific RNAi targeting Ca-1T and Slowpoke in gliomas reduces glioma cell number and membrane extension and decreases glioma cell Ca{superscript 2} activity and downstream activation of PI3K and pRIII/pERK signaling. Moreover, Slowpoke knockdown significantly extends glioma fly survival to near-control values and improves glioma-associated neurodegeneration. RNAseq transcriptomic analysis reveals shared regulation by both channels of pathways involved in metabolic rewiring, cell adhesion and excitatory neurotransmission, while uncovering distinct effects on synaptic function. ConclusionsBoth Ca-1T and Slowpoke are essential for pro-tumorigenic Ca{superscript 2}-dependent signaling in Drosophila gliomas. Common effects observed upon gene knockdown support a coordinated function for these channels at the plasma membrane. Nevertheless, their distinct impacts on survival and gene expression profiles highlight non-redundant roles. Notably, Slowpoke knockdown promotes increased survival and neuroprotection, associated with the repression of synaptic genes aberrantly upregulated in gliomas, thereby identifying Slowpoke as a promising therapeutic target in glioblastoma.

cancer biology↗

bioRxiv2021

Sensitive high-throughput assays for tumour burden reveal the response of a Drosophila melanogaster model of colorectal cancer to standard chemotherapies

Drosophila melanogaster (Drosophila) models of cancer are emerging as powerful tools to investigate the basic mechanisms underlying tumour progression and identify novel therapeutics. Rapid and inexpensive, it is possible to carry out genetic and drug screens at a far larger scale than in vertebrate organisms. Such whole-organism-based drug screens permits assessment of drug absorption and toxicity, reducing the possibility of false positives. Activating mutations in the Wnt and Ras signalling pathways are common in many epithelial cancers, and when driven in the adult Drosophila midgut, it induces aggressive intestinal tumour-like outgrowths that recapitulate many aspects of human colorectal cancer (CRC). Here we have taken a Drosophila CRC model in which tumourous cells are marked with both GFP and luciferase reporter genes, and developed novel high-throughput assays for quantifying tumour burden. Leveraging these assays, we find that the Drosophila CRC model responds rapidly to treatment with standard CRC-drugs, opening the door to future rapid genetic and drug screens.

cancer biology↗

bioRxiv2017

The Relationship Between Cancer Progression And Social Environment In Drosophila

The influence of oncogenic phenomena on the ecology and evolution of animal species is fast becoming an important research topic. Similar to host-pathogen interactions, cancer negatively affects host fitness, which should lead to the selection of host control mechanisms, including behavioral traits that best minimize the proliferation of malignant cells. Social behavior is one such trait, which is suggested to influence cancer progression. While the ecological benefits of sociality in gregarious species are widely acknowledged, only limited data are available on the role of the social environment on cancer progression. Here, we exposed adult Drosophila, with colorectal-like tumors, to different social environments. First, we show that cancerous flies kept in complete isolation exhibit increased tumor progression. Yet, more surprisingly, we find that cancerous flies, kept in groups with other noncancerous individuals, also develop tumors at a faster rate compared to those kept with other cancerous conspecifics, suggesting a strong impact of social group composition on cancer growth. Finally, we show that flies can discriminate between individuals at different stages of tumor growth and selectively choose their social environment accordingly. Control flies actively avoid flies with cancer but only at the later stages of tumor development, whereas cancerous flies display strong social interactions with cancerous flies in the early stages of tumor growth. Our study demonstrates the reciprocal links between cancer and social interactions, as well as highlighting how sociality impacts health and fitness in animals and its potential implications for disease ecology and ecosystem dynamics.

animal behavior and cognition↗