Why Don’t Naked Mole Rats get Cancer?

Naked mole rat

Naked mole rats are the most fascinating of creatures. There are many reasons I say this, but today I want to focus on one particular feature about them that is just an amazing example of how weird and wonderful they are. Naked mole rats are extremely resistant to cancer – tumors have never been observed in them. How on earth do they manage this?

✤ Before I explain the exact mechanism, we need to go over some basics. A tumor is an aggregation of cells. Cells generally don’t like to be too close to each other – in the lab, if a petri-dish has too many cells on it, the overcrowding makes them stop growing. We call this contact inhibition. The cells sense that they are too close to each other and secrete signaling molecules into their surroundings known as anti-growth factors. These molecules signal the cells to stop dividing. I explained this pathway in detail here. Cancer happens when this mechanism fails.

✤ If cancer happens when contact inhibition fails, then it logically follows that enhanced contact inhibition should mean even more cancer resistance. Bingo – that is exactly what happens with naked mole rat cells. These cells are hypersensitive to contact inhibition, which is what makes them so resistant to cancer.

✤ Our cells also have a mechanism for contact inhibition, and yet we are unfortunately more than capable of developing cancer. This raises the question, what is so special about naked mole rat cells that makes them so hypersensitive to contact inhibition?

✤ It turns out that naked mole rat cells have an additional mechanism to make them hypersensitive to contact inhibition. Our cells rely on a protein known as p27 to halt cell division by putting the brakes on the cell cycle. Naked mole rat cells, on the other hand, use p27 for regular contact inhibition just like we do and another protein known as p16 for early contact inhibition. The naked mole rat cells have the same genes we do (we both have p27 and p16) but their functions are distinct; for naked mole rats, p16 functions as the ‘early brake’ while p27 functions as the ‘backup brake’. There are other differences between our cells and naked mole rat cells, but this is the primary mechanism by which they evade cancer.

I find this work fascinating, not just because it features the awesome naked mole rat, but because it explains the molecular mechanism of why naked mole rats don’t get cancer. It also shows how the same genes are capable of vastly different functions in different species; although the naked mole rat’s anticancer defense strategy evolved separately to us, our cells carry the same tools.

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