Red cilia extend from cells that will develop into the embryo (labelled blue). Cells labelled in green won’t form the embryo, but instead they make up structures that surround it as it grows. These cells don’t have cilia. Courtesy of Dr Fiona Bangs
Cells are controlled by the relay of thousands of different messages.
These messages flow from outside the cell to inside (and vice versa), causing the cell to grow, divide, or in some cases die.
These processes go wrong in cancer cells. Some messages become hyped up, while other restraint signals are ignored.
One way cancer cells can ignore these signals is to get rid of the machinery that recognises them. And finger-like structures called primary cilia are part of this machinery.
Cilia are found on the surface of almost all cells. But they’re missing from most cancer cells.
They act like antennae, receiving messages from the world around them. Relaying these signals puts the brakes on processes that cancer cells need to grow. So it makes sense that these antennae are often missing in tumours.
“If cancer cells lose their cilia then they become deaf to restrictive signals, which could allow them to grow when they shouldn’t,” says Dr Fiona Bangs, a Cancer Research UK-funded scientist at the University of Oxford who captured the images in this post. “How cilia formation is regulated in cancer is only just beginning to be understood.”
Pointing the finger
The images shown here were made by Bangs when she was investigating cilia at the Memorial Sloan Kettering Cancer Center in New York.
They show mouse embryos that are 1-2 weeks old, and help track how cilia formation is controlled as the embryos develop. Studying how complex cellular messages work in early development can give clues about how and why these processes go wrong in cancer.
The images were made using fluorescent tags that stick to molecules in different parts of the embryo and show up on a microscope.
This makes cells that go on to form the embryo look blue, surrounded by cells that go on to form the placenta and non-embryonic tissues glowing green.
They also added a fluorescent tag to a molecule only found in primary cilia, making them look red. With this they’re able to see the cilia reaching out from cells like fingers to sense what’s going on around them.
Bangs was surprised by what she saw when she first captured this image.
Cilia had been thought to be present on pretty much all cells. But here, they were only seen on the blue embryonic cells, and they were missing on all the green non-embryonic cells.
And this wasn’t because the green cells lacked the components needed to make cilia. So it was unclear why the cilia weren’t there.
The answer came when another member of the lab found that a gene called Aurora kinase A (AurkA) was being produced at high levels inside the non-embryonic cells.
AurkA plays a part in the process that disassembles cilia. And Bangs thought that if these signals were switched on it might be responsible for the ‘missing’ cilia.
To test this she blocked the signals by switching off AurkA with a drug. Cilia began appearing on the surface of some of the non-embryonic cells, showing for the first time that these signals – called the cilium disassembly pathway – stop cilia from forming in non-embryonic cells.
So what does this mean for cancer?
It’s still early days for what’s known about how cilia are controlled. But similar to in non-embryonic cells, AurkA is also produced at high levels in a number of cancers, including pancreatic, breast and liver tumours. Bangs’ work suggests that it might be involved in cancer cells losing cilia as well.
“I’m now looking at whether turning on the cilium disassembly pathway when cells become cancerous can account for their cilia loss,” she says. And the next step is to test if cancer cells losing their cilia plays a role in their uncontrolled growth.
Bangs hopes that she’ll be able to use this knowledge to switch cilia formation back on in cancer cells in the lab.
And if this works, those fixed antennae could offer a way to make cancer cells listen to restraint signals once more.