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Cofilin-1 (CFL1) overexpression in pancreatic cancer correlates with high invasiveness and shorter survival. Besides a well-documented role in actin remodeling, additional cellular functions of CFL1 remain poorly understood. Here, we unraveled molecular tumor-promoting functions of CFL1 in pancreatic cancer. For this purpose, we first show that a knockdown of CFL1 results in reduced growth and proliferation rates in vitro and in vivo, while apoptosis is not induced. By mechanistic modeling we were able to predict the underlying regulation. Model simulations indicate that an imbalance in actin remodeling induces overexpression and activation of CFL1 by acting on transcription factor 7-like 2 (TCF7L2) and aurora kinase A (AURKA). Moreover, we could predict that CFL1 impacts proliferation and apoptosis via the signal transducer and activator of transcription 3 (STAT3). These initial model-based regulations could be substantiated by studying protein levels in pancreatic cancer cell lines and human datasets. Finally, we identified the surface protein CD44 as a promising therapeutic target for pancreatic cancer patients with high CFL1 expression.

Hematopoietic stem cells (HSCs) provide all types of blood cells during the entire life of the organism. HSCs are mainly quiescent and can eventually enter the cell cycle to differentiate. HSCs are maintained and tightly regulated in a particular environment. The stem cell niche regulates dormancy and awakening. Deregulations of this interplay can lead to hematopoietic failure and diseases. In this paper, we present a Boolean network model that recapitulates HSC regulation in virtue of external signals coming from the niche. This Boolean network integrates and summarizes the current knowledge of HSC regulation and is based on extensive literature research. Furthermore, dynamic simulations suggest a novel systemic regulation of TP53 in homeostasis. Thereby, our model indicates that TP53 activity is balanced depending on external stimulations, engaging a regulatory mechanism involving ROS regulators and RAS activated transcription factors. Finally, we investigated different mouse models and compared them to in silico knockout simulations. Here, the model could recapitulate in vivo observed behaviors and thus sustains our results.

In its most trending interpretation, empowerment in health care is implemented as a patient-centered approach. In the same sense, many mobile health (mHealth) apps are being developed with a primary focus on the individual user. The integration of mHealth apps into the health care system has the potential to counteract existing challenges, including incomplete or nonstandardized medical data and lack of communication, especially in the intersectional context (eg, patients, medical forces). However, concerns about data security and privacy, regional differences in regulations, lack of accessibility, and nontransparent apps hinder the successful integration of mHealth into the health care system. One approach to address this is to rethink the interpretation of empowerment. On that basis, we here examine existing approaches of individual empowerment and subsequently analyze a different view of empowerment in digital health, namely interaction empowerment. Such a change of perspective could positively influence intersectoral communication and facilitate secure data and knowledge sharing. We discuss this novel viewpoint on empowerment, focusing on more efficient integration and development of mHealth approaches. A renewed interpretation of empowerment could thus buffer current limitations of individual empowerment while also advancing digitization of the health system.