Actin affects the spread of cancer in several ways – ScienceDaily

Metastasis occurs when cancer cells leave the primary tumor and spread throughout the body. For this, they have to sever connections with neighboring cells and migrate to other tissues. Both processes are enhanced by signaling molecules released by tumor cells, which consequently increase the malignancy of tumors. A research team led by Prof. Dr. Robert Gross and Dr. Carsten Schwann from the University of Freiburg found that the release of these so-called factors is affected by the skeleton of cells. The study has been published in advanced science.

Actin has several functions in the spread of cancer

Actin filaments are part of the cell’s skeleton and are essential for stability and motility. It forms a network that is dynamically formed and broken down by the addition or separation of building blocks at the ends of the filaments. These processes are finely regulated by other molecules, such as the so-called formin. The dynamics of the actin network enables cell movement, for example during development or wound closure, but also during metastasis of cancer cells. Actin also plays a role in transporting materials within the cell. However, this is less understood than other mechanisms of intracellular transport.

The Freiburg researchers have now found that the actin network also enables the release of prometastatic factors. In their study, they used high-resolution microscopy to track the movement of individual transport vesicles inside living cancer cells. “We have observed that vesicles loaded with ANGPTL4 move to the periphery of the cell by dynamic and local polymerization of actin filaments,” says Gross, who is a member of the CIBSS Excellence Group – Center for Integrative Biological Signaling Studies at the University of Freiburg. ANGPTL4 is an important prostate factor that promotes metastasis formation in various types of cancer.

FMNL2 controls the transport of ANGPTL4 along actin filaments

Based on microscopic observations and genetic analyses, the scientists concluded that the movement of vesicles is controlled by the formin-like molecule FMNL2 by initiating the polymerization — that is, elongation — of actin filaments directly in the vesicle. “We already knew that increased FMNL2 activity has etiological effects in many types of tumors,” says Gross. “In our current work we can now show an important underlying process and connection of the TGFbeta signaling pathway.” According to the scientist, this knowledge can be used to diagnose tumors or treat. For example, by developing an antibody that signals the presence of active FMNL2 or pharmacologically targeting active and phosphorylated FMNL2.

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