Lung Cancer Metastases Controlled by Molecular Actions in ‘Cellular Post Office’

Lung Cancer Metastases Controlled by Molecular Actions in ‘Cellular Post Office’

A molecular signal in a cellular compartment often referred to as the cell’s “post office” explains how lung cancer cells gain the ability to leave the lung tissue and cause metastases — an insight that may allow researchers to search for ways to prevent this from happening.

The study, Epithelial-to-mesenchymal transition drives a pro-metastatic Golgi compaction process through scaffolding protein PAQR11,” was published in the Journal of Clinical Investigation.

Researchers from the University of Texas MD Anderson Cancer Center discovered the signal within the Golgi apparatus. This structure, which is composed of stacks of membranes, is the key distributor of proteins destined to be used both within and outside the cell. The Golgi apparatus packages the proteins in tiny sacs that detach from the membranes of the structure.

Scientist knew that the Golgi apparatus could appear either as a compact structure close to the cell nucleus or as a loose system of membranes. Although the research team suspected that the change in appearance might be linked to cancer spread, they had not investigated it until now.

The team found that a process called endothelial to mesenchymal transition, whereby cells gain the ability to detach from tissue, is linked to a more compact state of the Golgi cellular compartment. In lung cancer cells from both mice and human patients, the team observed that a factor called Zeb1 released during the transition from attached to migratory cells interacted with a Golgi protein called PAQR11.

The interaction turned out to be a signal for the cell to change the delivery routes of the protein-containing sacs, ultimately leading to changes in the cell appearance that allow it to move to other parts of the body to form metastases.

“We concluded that, through PAQR11, tumor cells can hijack a normal Golgi compaction process in order to gain metastatic ability,” Jonathan Kurie, MD, professor of thoracic head and neck medical oncology at MD Anderson and senior author of the study, said in a news release.

Dr. Daniel Ungar, from the Department of Biology at the University of York in the United Kingdom, and one of the study’s co-authors, explained the process allowing cancer metastases in a less scientific manner.

“If we think of the cancer cell like a tent structure, it has fixed sides to hold its shape and is firmly anchored to the ground in order to secure its contents. It cannot conceivably be moved until its architecture is altered somehow,” he said.

“In order to move the tent, we have to rearrange its contents and collapse its sides … to lift it out of its anchored position and carry it away. A similar process happens with cancer when it metastasizes — its outer edges are altered resulting in it becoming unanchored,” Ungar added.

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