Cell Cannibalism May Lead to Cancer Control Therapy

An unexpected link between cell division and cell cannibalism (entosis), which is relevant to both cancer and chemotherapy, was described in a recent paper.

Entosis is a form of epithelial cell cannibalism that is prevalent in human cancer, typically triggered by loss of matrix adhesion. In the laboratory, entosis has only been seen in cells that are detached from their surroundings. Cells in the body are typically surrounded and supported by a mesh of proteins called the extracellular matrix. However, within a tumor, cancer cells can often begin to grow without being attached to the matrix, which means that entosis can occur. A protein called Cdc42 (Cell division control protein 42 homolog) plays a part in how cells attach to each other and to the extracellular matrix, but the role of Cdc42 in controlling entosis had not been previously explored.

Investigators at the Babraham Institute (Cambridge, United Kingdom) initially set out to ask whether Cdc42 was involved in the established process of cell cannibalism, as seen in detached cells. However, the experiments showed that removing Cdc42 from human cells grown in the laboratory had little effect on this method of entosis.

On the other hand, the loss of Cdc42 did enable a different form of entosis in cells that remained attached to the extracellular matrix, which had not been seen before. This new process of entosis was linked to cell division (mitosis), with cells that were dividing or that had recently divided being consumed by neighbors.

During cell division a group of proteins - including RhoA and myosin - cause cells to become rounder and stiffer, allowing the dividing cells to force their way inside other cells. This is the key first stage of entosis. Since cancer cells divide often, this form of cell cannibalism may lead to the cancer cells being destroyed by their healthy neighbors, in a form of “assisted suicide”. This form of entosis is more commonly seen in cancers where the cells divide frequently, and some chemotherapy drugs that interfere with cell division also increase the rate of cell cannibalism.

Senior author Dr. Oliver Florey, a researcher at the Babraham Institute, said, "Entosis is a fascinating process that may play a role in normal physiology, as well as cancer. By studying entosis, we hope to gain insights into fundamental cell biology, as well as to explore intriguing new avenues for cancer research. After 100 years of observing "cell-in-cell" structures, there is now an exciting push towards discoveries in both cell and cancer biology."

The mitosis entosis study was published in the July 11, 2017, online edition of the journal eLife.

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Babraham Institute