Summary of A Protein That Helps Drive Cancer Metastasis:
Freiburg researchers have demonstrated that the transport of molecules along the cell’s skeleton plays a crucial role in cancer metastasis. They found that the release of prometastatic factors, which drive the malignancy of tumors, is influenced by the cells’ skeleton. The actin filaments, which form a network that dynamically builds up and gets broken down, are essential for stability and motility and enable the locomotion of cells and the transport of substances within the cell. The research team observed that the formin-like molecule FMNL2 initiates polymerization of actin filaments directly at the vesicle, controlling the movement of the vesicles containing ANGPTL4, an important prometastatic factor that promotes the formation of metastases in various types of cancer. This knowledge could be used for tumor diagnostics or therapy.
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Cancer Metastasis: How the Transport of Molecules Along the Cell’s Skeleton Plays a Crucial Role
Cancer is a disease that affects millions of people worldwide. It is characterized by the uncontrolled growth of abnormal cells that can invade surrounding tissues and spread to other parts of the body. This process, known as metastasis, is a major cause of death due to cancer. In order to better understand and potentially treat metastasis, researchers have been studying the mechanisms that drive its progression.
A team of researchers led by Professor Robert Grosse and Dr. Carsten Schwan from the University of Freiburg recently discovered that the release of prometastatic factors, which drive the malignancy of tumors, is influenced by the cells’ skeleton. The findings were published in the journal Advanced Science.
Actin has several functions in cancer propagation
Actin filaments are part of the cell skeleton and essential for stability and motility. They form a network that dynamically builds up and gets broken down by the addition or detachment of building blocks at the filaments’ ends. These processes are precisely regulated by other molecules, such as so-called formins.
The dynamics of the actin-network enable the locomotion of cells, for example during development or wound closure, but also that of spreading cancer cells. Actin also plays a role in the transport of substances within the cell. However, this is less well understood than that of other intracellular transport mechanisms.
The Freiburg researchers now found that the actin-network also enables the release of prometastatic factors. For their study, they used high-resolution microscopy to track the movement of individual transport vesicles within living cancer cells.
“We observed that ANGPTL4-loaded vesicles are conveyed to the periphery of the cell by means of dynamic and localized polymerization of actin filaments,” says Grosse, who is a member of the Cluster of Excellence CIBSS – Centre for Integrative Biological Signalling Studies at the University of Freiburg.
ANGPTL4 is an important prometastatic factor that promotes the formation of metastases in various types of cancer.
FMNL2 controls the transport of ANGPTL4 along actin filaments
Based on the microscopic observations and genetic analyses, the scientists conclude that the vesicles’ movement is controlled by the formin-like molecule FMNL2 by initiating polymerization – i.e. elongation – of actin filaments directly at the vesicle.
“We already knew that increased FMNL2 activity has prometastatic effects in many types of tumors,” says Grosse. “In our current work, we could now demonstrate an important underlying process and a connection to the TGFbeta signaling pathway.”
According to the scientist, this knowledge could be used for tumor diagnostics or therapy. for example, by developing an antibody that indicates the presence of active FMNL2 or pharmacologically targets active, phosphorylated FMNL2.
The findings of this study are significant as they demonstrate the important role that the transport of molecules along the cell’s skeleton plays in cancer metastasis. This could potentially lead to new treatments for this deadly disease.
