Role of the Planar Cell Polarity and Mitochondria Crosstalk in Fuelling Cell Migration

Project Identification
MUNI/J/0004/2021
Project Period
1/2022 - 12/2024
Investor / Pogramme / Project type
Masaryk University
MU Faculty or unit
Faculty of Science

In this project, I and my research team will investigate the physical and functional crosstalk between WNT/Planar Cell Polarity (PCP) and mitochondrial signalling during cell migration. Cell migration plays a central role in both vertebrate morphogenesis and pathogenic conditions (such as metastatic cells in cancer), and requires energy that is provided by mitochondria, e.g., in the form of ATP. There is accumulating evidence that cell migration is directed by PCP, a fundamental property of cells in multicellular organisms providing directional and positional information. Currently, whether and how PCP is interconnected with mitochondrial signalling, and whether migrating cells can obtain energy via PCP signalling necessary for cell migration, remains unknown. More importantly, we largely lack insight into bioenergetic processes underlying the preparation of a cell for its subsequent migration.

Here, I am suggesting that a) the PCP proteins Vangl and Prickle instruct mitochondria to produce ATP or other high-energy compounds, and b) such process is relevant for cell migration on the example of the Xenopus model organism and mammalian cell migration. Confirming this central hypothesis would be a breakthrough discovery illuminating the guiding principle and logic of cell migration. Such principle, if correct, is likely exploited also by many types of metastatic cells in vivo and thus profoundly enhancing the interdisciplinary potential of this project. In sum, the proposed study will open up new avenues for basic research as well as it has great potential for clinical use.

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