Gene Discovery May Offer Therapy to Slow Mesothelioma

Researchers at the Salk Institute in La Jolla, California, think they’ve stumbled onto a gene partnership that, when it fails, lets mesothelioma cells move throughout your body.

Keeping this gene partnership intact could therefore be a way to slow or even stop the spread of mesothelioma, they say.

The researchers’ findings were reported in a recent issue of the journal Molecular Cell.

Normal cells don’t roam around, but mesothelioma cells do. The reason for this is that mesothelioma cells possess the means of altering a structure known as the focal adhesion complex.

Every cell has one of these structures.

Normal cells can’t do anything to change the focal adhesion complex, which moors each cell to every one of its immediate neighbors. As a result, none of them go anywhere.

Mesothelioma Plays a Dirty Trick

It’s been known for a while that a gene labeled LKB1 is present in healthy cells but often missing in cancer patients.

What was not previously known is that LKB1 plays a role in managing the focal adhesion complex.

Something else not previously known is that LKB1 talks to another gene, DIXDC1, about things that need to be done with regard to focal adhesion complex management.

In the conversations these two genes have with each other, LKB1 lets DIXDC1 know the status of the focal adhesion complex’s operation.

DIXDC1 tells LKB1, “Hey, good job keeping an eye on things,” and then gives LKB1 some feedback on how big or small to make the complex and how many more or fewer adhesions are needed.

In this relationship, DIXDC1 is essentially the management guy and LKB1 is the shop foreman. Or, expressed another way, DIXDC1 is the skipper and LKB1 is the chief petty officer.

The researchers figured out that the reason why LKB1 goes stops working when cancer shows up is because the cancer tells it to.

More precisely, mesothelioma causes DIXDC1 to stop communicating with LKB1.

Instead, the cancer impersonates DIXDC1 and tells LKB1 to shut down.

With no one in charge of the operation, the focal adhesion complex machinery runs wild. The focal adhesions shrink and loosen their grip on the surrounding cells.

At that point, the mesothelioma cell breaks free of its mooring and drifts away.

A Way to Stop Mesothelioma

It may even be worse than that.

Apparently, the leaderless focal adhesion complex appears to give the unmoored cancer cell a shove to send it on its way.

The researchers contend in their article that the way to solve this problem is to reestablish the communication between DIXDC1 and LKB1.

Their thinking is that by getting these two to once more work together, the focal adhesion complex will operate correctly and mesothelioma won’t be able to cast off its mooring lines.

This, say the researchers, opens the door to the possibility that a gene therapy — yet to be devised — could target DIXDC1 in patients whose cells have turned cancerous or soon will.