Perturbation-Based Modeling Unveils the Autophagic Modulation of Chemosensitivity and Immunogenicity in Breast Cancer Cells

In the absence of new therapeutic strategies, chemotherapeutic drugs are the most widely used strategy against metastatic breast cancer, in spite of eliciting multiple adverse effects and having low responses with an average 5-year patient survival rate. Among the new therapeutic targets that are currently in clinical trials, here, we addressed the association between the regulation of the metabolic process of autophagy and the exposure of damage-associated molecular patterns associated (DAMPs) to immunogenic cell death (ICD), which has not been previously studied. After validating an mCHR-GFP tandem LC3 sensor capacity to report dynamic changes of the autophagic metabolic flux in response to external stimuli and demonstrating that both basal autophagy levels and response to diverse autophagy regulators fluctuate among different cell lines, we explored the interaction between autophagy modulators and chemotherapeutic agents in regards of cytotoxicity and ICD using three different breast cancer cell lines. Since these interactions are very complex and variable throughout different cell lines, we designed a perturbation-based model in which we propose specific modes of action of chemotherapeutic agents on the autophagic flux and the corresponding strategies of modulation to enhance the response to chemotherapy. Our results point towards a promising therapeutic potential of the metabolic regulation of autophagy to overcome chemotherapy resistance by eliciting ICD.Universidad de Costa Rica/[803-B6-600]/UCR/Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Enfermedades Tropicales (CIET)UCR::Vicerrectoría de Docencia::Salud::Facultad de Microbiologí

Supplemental Material for A contribution to Cerataphis molecular taxonomy and ecology: the Costa Rican case

Index of supplemental materials: Table S1. Species information and accession number for sequences retrieved from public databases included in phylogenetic analysis. Table S2. Uricase (urate oxidase) partial sequences for YLS obtained from C. brasiliensis and C. orchidearum, and four Fulgoroidea species samples in Costa Rica. Table S3. Ant species associated with colonies of Cerataphis spp. and plant host combinations observed in Costa Rica and/or reported worldwide.Peer reviewe

A contribution to Cerataphis molecular taxonomy and ecology: the Costa Rican case

The aphid genus Cerataphis Lichtenstein is native to Southeast Asia although several species have been distributed to other tropical regions of the world. Cerataphis brasiliensis (Hempel) and Cerataphis lataniae (Boisduval) are of interest due to their potential as pests on palms. Those species and Cerataphis orchidearum (Westwood) may be morphologically confused with each other. In Costa Rica, two species have been reported, C. brasiliensis and C. orchidearum. This work aimed to contribute molecular data and ecological observations for species of Cerataphis present in Costa Rica. Few colonies (low frequency of occurrence) of C. brasiliensis and C. orchidearum were recorded during a survey conducted during 2014. Ten ant species were found associated to these aphid colonies. Partial sequences for the genes COI and EF-1α were obtained and compared to the few sequences available for this genus in public databases. Species identification by COI (barcoding) was not conclusive. Phylogenetic analyses and similarity pairwise comparisons showed a close relationship with the genus Tuberaphis Takahashi, including the clustering of mixed species from both genera. Yeast-like symbionts were detected by PCR in individuals of both Cerataphis species found in Costa Rica. Overall, the results suggest there is a need of curated sequence data representing the different Cerataphis species worldwide.This research was funded by Universidad de Costa Rica (grants 801-B7-169 and 801-A1-801). The authors are thankful to Carolina Godoy Cabrera, Universidad Estatal a Distancia, Costa Rica, for identification of delphacid individuals.Peer reviewe