Researchers from the University of Freiburg found that the release of so-called prometastatic factors is influenced by proteins in the cells’ skeleton called actin.
According to the research team, led by Dr Robert Grosse and Dr Carsten Schwan, the transportation of actin molecules along the cell’s skeleton plays a role in the spread of cancer metastasis
Metastases occur when cancer cells leave the primary tumour and spread throughout the body. For this to happen the cells have to break contact with neighbouring cells and move to other tissues. These processes are aided by signalling molecules released by cancerous cells, which increase the malignancy of the tumour.
The study has been published in the journal Advanced Science.
What is actin?
Actin filaments make up part of the cell skeleton and are important for stability and mobility. Actin forms a network that is built up and broken down through the addition or detachment of building blocks at the filaments’ end.
This process is regulated by other molecules, known as formins. The actin network enables the movement of cells throughout the body, for example during wound closure, and this process also happens in the spreading of cancer cells. Actin also facilitates the transportation of substances within the cell.
The researchers have discovered that the actin network causes the release of prometastatic factors. In their study, the researchers used high-resolution microscopy to monitor the movement of individual transport vesicles inside living cancer cells.
“We observed that ANGPTL4-loaded vesicles are conveyed to the periphery of the cell by means of dynamic and localised polymerisation of actin filaments,” said Grosse, who is a member of the Centre for Integrative Biological Signalling Studies (CIBSS) at the University of Freiburg.
ANGPTL4 promotes the formation of metastases in various types of cancer and is an important premetastatic factor.
The findings could facilitate new diagnostic
The researcher’s microscopic observations and genetic analyses led them to conclude that the movement of vesicles is controlled by the formin-like molecule FMNL2 through polymerisation. Polymerisation describes the elongation of actin filaments within the vesicle.
“We already knew that increased FMNL2 activity has prometastatic effects in many types of tumours. In our current work we could now demonstrate an important underlying process and a connection to the TGF-beta signalling pathway,” said Grosse.
The researchers say this knowledge could be used in tumour diagnostics and therapy. The findings could help the development of an antibody capable of indicating the presence of active FMNL2 and targeting active phosphorylated FMNL2.
This research comes as part of a series of studies from CIBBS. CIBSS are aiming to achieve a comprehensive understanding of the biological signalling processes. They want to better our understanding of interactions between individual molecules and cells, as well as processes in organs and organisms.
The researchers say they will use the knowledge gained to develop strategies for controlling signals in a targeted way. New technologies could enable them to gain new insights into research and develop innovations in medicine and plant sciences.