ERK signaling code of epithelial morphogenesis and cancer
- Project Identification
- Project Period
- 4/2021 - 12/2023
- Investor / Pogramme / Project type
- Masaryk University
- MU Faculty or unit
- Faculty of Medicine
- Other MU Faculty/Unit
- Faculty of Informatics
ERK signaling plays a crucial role in regulation of key cellular processes, including proliferation, differentiation, migration, survival, and death. Thereby, ERK signaling is essential for tissue development, and dysregulation of ERK signaling leads to cancer. But how does signaling activity of one molecule, ERK, defines so many diverse outcomes? Current evidence suggests that the information for very specific cellular responses is encoded in complex spatiotemporal patterns of the activity of ERK molecules – oscillations of various amplitude, frequency and duration, that are only beginning to become understood. It remains largely elusive, how ERK signaling executes the divergent functions during the complex events of organ development and tumorigenesis. We hypothesize that specific patterns of ERK signaling dynamics and their coordination across tissue encode distinct morphological processes during tissue development, determine different cancer cell behaviors, and confer differences in cancer therapeutic susceptibilities and prognosis.
In this interdisciplinary project we aim to decipher the ERK signaling code in mammary epithelial morphogenesis and cancer using state-of-the-art imaging of mammary organoids with ERK biosensor, automated analysis of large imaging data, deep computational analysis of the temporal ERK activity fluctuations and the associated cellular fates, mathematical modeling of signal transduction, and perturbation analysis.
This multidisciplinary study will contribute to understanding of signaling principles of the crucial ERK pathway. In the era of single-cell techniques and precision medicine, our findings will provide in-depth information on cell fate encoding by ERK signaling dynamics and mechanisms of normal and neoplastic breast cell heterogeneity, with the potential application in development of new rational, tailored treatment strategies and predictions of therapeutic responses.