How cells become invasive is a scientific mystery. Cell invasion is a process in which a cell crosses a basement membrane, a thin, dense, sheet-like matrix that lines tissues and gives your body support. Scientists know that cells have to invade several times during development in an embryo to form organs and tissues, but the reason why certain cells become invasive while others do not is undetermined.
David Q. Matus, an assistant professor in the Department of Biochemistry and Cell Biology at Stony Brook University, studies the process of cell invasion and its misregulation in certain diseases, such as cancer metastasis. In a recent study published in Developmental Cell, Matus discovered that cells cannot divide and invade at the same time.
“When people think of cell invasion, they usually think about cancer,” Matus said. “Cells have to escape the primary tumor so they have to invade through basement membrane to do that. They have to then get into your blood vessels, leave your blood vessels, and then invade to the next place.”
To study the process of cell invasion, Matus designed an experiment using anchor cells from C. elegans, a roundworm nematode. These cells are naturally invasive and do not divide.
“The anchor cell’s job is to, during development, make a connection between the developing uterine tissue and the developing vulva tissue so that the worm can lay eggs, and it does that by invading through the basement membranes that are separating them,” Matus said. “It’s really the only model that you can look at in a lab where you can look an invading cell and the surrounding basement membrane.”
Matus began the experiment by trying to answer the simple question of how anchor cells become invasive, and he ended up discovering more than he anticipated.
“I didn’t go in saying, ‘I want to test whether cells can’t divide and invade at the same time,’ and in fact if I probably tried to do that experiment, I wouldn’t have been able to figure it out,” Matus admitted. “Instead we were just trying to let the worm tell us how this cell becomes invasive.”
To determine how anchor cells become invasive, Matus used genetic screening to determine which transcription factor, a protein that turns genes on and off, was most likely providing the anchor cells with the necessary tools to become invasive. From the screening tests, he determined that the transcription factor important for cell invasion also prevents the anchor cell from dividing. In particular, it halts the cell in the G1 phase of the cell cycle.
“The key experiment that I did to prove that cell division and cell invasion are mutually exclusive was I took a mutant for this transcription factor where you have dividing anchor cells and I blocked cell division, and when I blocked cell division those cells became invasive,” Matus said. ”So it wasn’t that you need the transcription factor to invade. It’s that the transcription factor’s job is to prevent the anchor cell from dividing.”
Matus’s discovery can open new doors to treating cancer. Current cancer treatments are designed to target cells that are constantly dividing, which can leave behind the nondividing invasive cells that can cause the cancer to spread. The idea of targeting invasive cancer cells is not a new one, but Matus’s research provides a better understanding of how to accomplish this.
“What my results suggest is maybe a new method of targeting invasive cells,” Matus said “Taking advantage of the fact that invasive cancer cells might be in G1, now we need to figure out how to target cells that are in G1.”