C. elegans Study Reveals Complex Process of Cell Invasion

A recent Duke University study conducted on C. elegans may help researchers better understand the process of metastasis. The team identified over 1,500 active genes in invasive cells that penetrate the basement membrane, describing their findings as the first “parts list” for a cell invading through tissue barriers. This process is the first step in metastasis, the process by which cancer cells break loose and spread throughout the body. 

For cancer cells to metastasize, they must first penetrate the basement membrane, a dense, sheet-like mesh of proteins and other molecules surrounding the tissues. However, this complex process has been challenging to study, as most cancer cells metastasize deep within the body, beyond the reach of light microscopes.

However, both C. elegans worm cells and human cancer cells rely on similar machinery to weaken and hack through tissue barriers. During a worm’s development, a specialized cell called the anchor cell must break through the tough membrane that separates the worm’s uterus from its vulva to clear a path for the worm to lay eggs.

For both humans and worms, enzymes act like molecular scissors to help cut through the mesh. Tiny foot-like projections sprout from the cell surface and pound away. Invading cells also make stiff networks of actin filaments for a harder-hitting punch.

By silencing 13 of the identified genes, the researchers could effectively slow cells down. They also found that the genes encoding the building blocks of ribosomes were particularly active and that, without ribosomes, invasive cells are cut off from the things they need.

The team also discovered that ribosome levels in cells surged in the hours leading up to invasion. By attaching a glowing tag to the ribosomes, the researchers were able to watch these cellular “protein factories” as they went about their business. The ribosomes of invading cells were then concentrated in the endoplasmic reticulum, where proteins are synthesized and packaged for transport.

These findings, published in Development, could help identify combinations of genes that, when knocked down together, might limit ribosome production and disrupt the cell invasion’s supply chain. The researchers hope that by studying the tools and tricks cells use to invade, they can identify more effective ways to put the brakes on cancer’s spread.