Maura Cárdenas-García

Modeling Intercellular Communication as a Survival Strategy of Cancer Cells: An In Silico Approach on a Flexible Bioinformatics Framework.

Intercellular communication is very important for cell development and allows a group of cells to survive as a population. Cancer cells have a similar behavior, presenting the same mechanisms and characteristics of tissue formation. In this article, we model and simulate the formation of different communication channels that allow an interaction between two cells. This is a first step in order to simulate in the future processes that occur in healthy tissue when normal cells surround a cancer cell and to interrupt the communication, thus preventing the spread of malignancy into these cells. The purpose of this study is to propose key molecules, which can be targeted to allow us to break the communication between cancer cells and surrounding normal cells. The simulation is carried out using a flexible bioinformatics platform that we developed, which is itself based on the metaphor chemistry-based model.

Applying the Tuple Space-Based Approach to the Simulation of the Caspases, an Essential Signalling Pathway

Apoptotic cell death plays a crucial role in development and homeostasis. This process is driven by mitochondrial permeabilization and activation of caspases. In this paper we adopt a tuple spaces-based modelling and simulation approach, and show how it can be applied to the simulation of this intracellular signalling pathway. Specifically, we are working to explore and to understand the complex interaction patterns of the caspases apoptotic and the mitochondrial role. As a first approximation, using the tuple spaces-based in silico approach, we model and simulate both the extrinsic and intrinsic apoptotic signalling pathways and the interactions between them. During apoptosis, mitochondrial proteins, released from mitochondria to cytosol are decisively involved in the process. If the decision is to die, from this point there is normally no return, cancer cells offer resistance to the mitochondrial induction.

Inspecting the Role of PI3K/AKT Signaling Pathway in Cancer Development Using an In Silico Modeling and Simulation Approach

PI3K/AKT signaling pathway plays a crucial role in the control of functions related to cancer biology, including cellular proliferation, survival, migration, angiogenesis and apoptosis; what makes this signaling pathway one of the main processes involved in cancer development. The analysis and prediction of the anticancer targets acting over the PI3K/AKT signaling pathway requires of a deep understanding of its signaling elements, the complex interactions that take place between them, as well as the global behaviors that arise as a result, that is, a systems biology approach. Following this methodology, in this work, we propose an in silico modeling and simulation approach of the PI3K class I and III signaling pathways, for exploring its effect over AKT and SGK proteins, its relationship with the deregulated growth control in cancer, its role in metastasis, as well as for identifying possible control points. The in silico approach provides symbolic abstractions and accurate algorithms that allow dealing with crucial aspects of the cellular signal transduction such as compartmentalization, topology and timing. Our results show that the activation or inhibition of target signaling elements in the overall signaling pathway can change the outcome of the cell, turning it into apoptosis or proliferation.

An in Silico Approach for Understanding the Complex Intercellular Interaction Patterns in Cancer Cells

Intercellular interaction allows cancer cells to preserve their malignance and through cell junctions to induce malignance in neighbouring cells and receive nutrients from them. The Wnt (wingless-related integration site) signalling pathway plays an important role in the formation of intercellular communications. In this work, we explore the complex interactions patterns of intercellular communication in cancer cells using an in silico modelling and simulation methodology developed by us. The proposed cellular signalling model, characterized by a multicompartmental nature, provides symbolic abstractions and accurate algorithms to model both intracellular and intercellular behaviours. In particular, in this work, we propose an in silico model and simulation of the formation of different communication channels, involving the Wnt signalling pathway. The final purpose of this study is to propose target molecules leading to break the communication between a cancer cell and surrounding normal cells. In this way, it is not necessary to carry out long series of different in vitro experiments, but only a few, because the focus should be only on the key molecules, which saves time and money. We observed, using in silico experiments, how the inhibition of Wnt signalling pathway prevents that the cells surrounding a cancerous cell are transformed.

In Silico Modeling and Simulation Approach for Apoptosis Caspase Pathways.

We revisit and improve in silico modeling and simulation approach of the apoptosis caspases pathways, initially developed for exploring and discovering the complex interaction patterns of apoptotic caspases and the mitochondrial role. Symbolic abstractions and algorithms of the in silico model were improved to allow dealing with crucial aspects of the cellular signal transduction such as cellular processes. Also, the particular model of extrinsic and intrinsic apoptotic signaling pathways was improved, increasing the number of reactions and using all kinetic parameters accurately calculated. Using the computational simulation tool BTSSOC-Cellulat, we were able to determine experimentally how the modulation of concentrations of proteins XIAP, cFLIPs and TRAIL/FASL, can cause the death of cancerous cells. Our results show how crucial were the improvements made in the in silico modeling approach, which in turn were reflected in the accuracy of the simulation and, therefore, in the significant value of the in silico experiments carried out.