Biology subjects

Casanova, J.

Publications and source records attributed to Casanova, J..

4 recordsLinked to original sources

bioRxiv2023

Unveiling the role of osteosarcoma-derived secretome in premetastatic lung remodeling

Lung metastasis represents the leading cause of osteosarcoma-related death. Progress in preventing lung metastasis is pretty modest due to the inherent complexity of the metastatic process and the lack of suitable models. Herein, we provide mechanistic insights into how osteosarcoma systemically reprograms the lung microenvironment for metastatic outgrowth using metastatic mouse models and a multi-omics approach. We found that osteosarcoma-bearing mice or those preconditioned with cell-secretome harbour profound lung structural alteration with airways damage, inflammation, neutrophil infiltration, and remodelling of the extracellular matrix with deposition of fibronectin and collagen by stromal activated fibroblasts for tumour cell adhesion. These changes, supported by transcriptomic and histological data, promoted and accelerated the development of lung metastasis. Comparative proteome profiling of the cell secretome and mouse plasma identified a large number of proteins engaged in the extracellular-matrix organization, cell-matrix adhesion, neutrophil degranulation, and cytokine-mediated signalling, which were consistent with the observed lung microenvironmental changes. Moreover, we identified EFEMP1, a secreted extracellular matrix glycoprotein, as a potential risk factor for lung metastasis and a poor prognosis factor in osteosarcoma patients.

cancer biology↗

bioRxiv2022

Antagonistic role of the BTB-zinc finger transcription factors Chinmo and Broad-Complex in the juvenile/pupal transition and in growth control

During development, the growing organism transits through a series of temporally regulated morphological stages to generate the adult form. In humans, for example, development progresses from childhood through to puberty and then to adulthood, when sexual maturity is attained. Similarly, in holometabolous insects, immature juveniles transit to the adult form through an intermediate pupal stage when larval tissues are eliminated and the imaginal progenitor cells form the adult structures. The identity of the larval, pupal and adult stages depends on the sequential expression of the transcription factors chinmo, Br-C and E93. However, how these transcription factors determine temporal identity in developing tissues is poorly understood. Here we report on the role of the larval specifier chinmo in larval and adult progenitor cells during fly development. Interestingly, chinmo promotes growth in larval and imaginal tissues in a Br-C-independent and -dependent manner, respectively. In addition, we found that the absence of chinmo during metamorphosis is critical for proper adult differentiation. Importantly, we also provide evidence that, in contrast to the well-known role of chinmo as a pro-oncogene, Br-C and E93 act as tumour suppressors. Finally, we reveal that the function of chinmo as a juvenile specifier is conserved in hemimetabolous insects as its homolog has a similar role in Blatella germanica. Taken together, our results suggest that the sequential expression of the transcription factors Chinmo, Br-C and E93 during larva, pupa an adult respectively, coordinate the formation of the different organs that constitute the adut organism.

developmental biology↗

bioRxiv2020

MiMSI - a deep multiple instance learning framework improves microsatellite instability detection from tumor next-generation sequencing

Microsatellite instability (MSI) is a critical phenotype of cancer genomes and an FDA-recognized biomarker that can guide treatment with immune checkpoint inhibitors. Recent work has demonstrated that next-generation sequencing data can be used to identify samples with MSI-high phenotype. However, low tumor purity, as frequently observed in routine clinical samples, poses a challenge to the sensitivity of existing algorithms. To overcome this critical issue, we developed MiMSI, an MSI classifier based on deep neural networks and trained using a dataset that included low tumor purity MSI cases in a multiple instance learning framework. On a challenging yet representative set of cases, MiMSI showed higher sensitivity (0.940) and auROC (0.988) than MSISensor(sensitivity: 0.57; auROC: 0.911), an open-source software previously validated for clinical use at our institution using MSK-IMPACT large panel targeted NGS data.

bioinformatics↗

bioRxiv2018

Blimp-1 mediates the temporal control of embryonic tube maturation

The specification of tissue identity during embryonic development requires precise spatiotemporal coordination of gene expression. Many transcription factors required for the development of organs have been identified and their expression patterns are known; however, the mechanisms through which they coordinate gene expression in time remain poorly understood. Here we show that hormone-induced transcription factor Blimp-1 participates in the temporal coordination of tubulogenesis in Drosophila melanogaster by regulating the expression of many genes involved in tube maturation. In particular, we demonstrate that Blimp-1 regulates the expression of genes involved in chitin deposition and F-actin organization. We show that Blimp-1 is involved in the temporal control of lumen maturation by regulating the beginning of chitin deposition. We also report that Blimp-1 represses a variety of genes involved in tracheal maturation. Finally, we reveal that the kinase Btk29A serves as a link between Blimp-1 transcriptional repression and apical extra-cellular matrix organization.

developmental biology↗