Cancer is an illness that impacts countless people worldwide. It is characterized by the unchecked development of irregular cells that can invade surrounding tissues and spread out to other parts of the body.
Freiburg researchers show that the transportation of molecules along the cells skeleton plays an essential function in cancer metastasis.
Transition takes place when cancer cells break free from a main tumor and spread throughout the body, needing them to sever connections with nearby cells and migrate to other tissues. Signifying particles released by the cancer cells drive both processes and thereby increase the malignancy of growths.
A team of researchers led by Professor Robert Grosse and Dr. Carsten Schwan from the University of Freiburg found that the release of prometastatic elements, which drive the malignancy of tumors, is influenced by the cells skeleton. The findings were released in the journal Advanced Science.
Actin has several functions in cancer propagation
Actin filaments belong to the cell skeleton and essential for stability and motility. They form a network that dynamically constructs up and gets broken down by the addition or detachment of structure obstructs at the filaments ends. These procedures are exactly controlled by other molecules, such as so-called formins.
The dynamics of the actin-network enable the locomotion of cells, for instance throughout advancement or wound closure, but also that of spreading cancer cells. Actin also plays a role in the transportation of substances within the cell. Nevertheless, this is less well understood than that of other intracellular transport systems.
Super-resolution microscopy image of a cell. With fluorescent markers, the prometastatic factor ANGPTL4 is identified in magenta, the molecule FMNL2 in green, and the actin cell skeleton in white. FMNL2 (green) induces the polymerization of actin filaments (white) at the vesicle, moving it forward.
The Freiburg scientists now found that the actin-network likewise allows the release of prometastatic factors. For their study, they used high-resolution microscopy to track the movement of specific transport blisters within living cancer cells.
” We observed that ANGPTL4-loaded vesicles are communicated to the periphery of the cell by means of localized and dynamic polymerization of actin filaments,” states 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 aspect that promotes the development of metastases in different types of cancer.
FMNL2 controls the transport of ANGPTL4 along actin filaments
Based on the tiny observations and hereditary analyses, the researchers conclude that the blisters movement is managed by the formin-like particle FMNL2 by starting polymerization– i.e. elongation– of actin filaments straight at the vesicle.
” We already knew that increased FMNL2 activity has prometastatic impacts in numerous types of growths,” says Grosse. “In our current work, we might now show an essential underlying process and a connection to the TGFbeta signaling pathway.”
According to the researcher, this understanding might be used for growth diagnostics or treatment. By developing an antibody that indicates the presence of active FMNL2 or pharmacologically targets active, phosphorylated FMNL2.
Reference: “Vesicle-Associated Actin Assembly by Formins Promotes TGFβ-Induced ANGPTL4 Cell, secretion and trafficking Invasion” by Dennis Frank, Jessica Christel Moussie, Svenja Ulferts, Lina Lorenzen, Carsten Schwan and Robert Grosse, 24 January 2023, Advanced Science.DOI: 10.1002/ advs.202204896.
Actin filaments are part of the cell skeleton and essential for stability and motility. The dynamics of the actin-network allow the mobility of cells, for example throughout advancement or injury closure, however likewise that of spreading cancer cells. Actin also plays a role in the transport of substances within the cell. Super-resolution microscopy image of a cell. With fluorescent markers, the prometastatic element ANGPTL4 is labeled in magenta, the molecule FMNL2 in green, and the actin cell skeleton in white.