New research from a team of Danish researchers shows how cancer cells can repair the damage that can otherwise kill them. Their findings are published in the journal Science Advances in a paper titled, “Restructuring of the plasma membrane upon damage by LC3-associated macropinocytosis.”

“The plasma membrane shapes and protects the eukaryotic cell from its surroundings and is crucial for cell life,” wrote the researchers. “Although initial repair mechanisms to reseal injured membranes are well established, less is known about how cells restructure damaged membranes in the aftermath to restore homeostasis. Here, we show that cells respond to plasma membrane injury by activating proteins associated with macropinocytosis specifically at the damaged membrane.”

The researchers damaged the membrane of the cancer cells using a laser that shoots small holes in the membrane and triggers macropinocytosis.

“Our research provides very basic knowledge about how cancer cells survive. In our experiments, we have also shown that cancer cells die if the process is inhibited, and this points towards macropinocytosis as a target for future treatment. It is a long-term perspective, but it is interesting,” explained group leader Jesper Nylandsted from the Danish Cancer Society’s Research Center and the University of Copenhagen, who has headed the new research and who for many years has investigated how cancer cells repair their membranes.

Previously, the researchers at the Danish Cancer Society demonstrated how cancer cells can use another technique to repair the membrane—by tying off the damaged part.

However, the experiments in the laboratory could indicate that especially the aggressive cancer cells use macropinocytosis. This may be due to the fact that the cancer cell has the opportunity to reuse the damaged membrane when it is degraded in the lysosomes. This type of recycling will be useful for cancer cells because they divide frequently, requiring large amounts of energy and material for the new cells.

“Our results suggest that cells actively replace parts of their plasma membrane upon injury and repair through macropinocytosis,” wrote the researchers. “The initial step to internalize damaged membrane by macropinocytosis appears to be the critical process for cell survival upon injury during restructuring. We propose that macropinocytosis enables cells to better cope with plasma membrane disruptions by removing wound areas containing both damaged membrane and proteins after initial repair. Thus, LAM supports the restructuring phase of the injury response, to fully reestablish plasma membrane integrity and homeostasis upon damage.”

The researchers are looking forward to continuing to investigate how cancer cells protect their membrane. This is explained by another member of the research team.

“We continue to work and investigate how cancer cells protect their membranes. In connection with macropinocytosis, in particular, it is also interesting to see what happens after the membrane is closed,” explained postdoc Stine Lauritzen Sønder, PhD. “We believe that the first patching is a bit rough and that a more thorough repair of the membrane is needed afterwards. It can be another weak point in the cancer cells, and is something we want to examine closer, she said.

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