Cholesterol makes cells’ nuclei squishy, helping melanoma spread Premium

Cholesterol enhances melanoma cell invasion by making nuclei squishier, revealing a potential treatment target in cancer progression.

Melanoma is one of the most dangerous common skin cancers. It starts in melanocytes, the skin cells that make melanin, the pigment that gives skin its colour.

Cancer doesn’t appear overnight. A normal cell becomes cancerous in steps, as its DNA and its gene-control systems pick up changes over time. These changes push the cell to do three things: divide too much, avoid being destroyed by the immune system, and spread into other parts of the body. This spread is called metastasis, and it is what makes many cancers deadly.

Researchers want to know which changes matter most because those changes can become targets for treatment.

A recent study led by scientists at the U.S. National Institutes of Health reported an unexpected driver of cancer spread: cholesterol in the membrane around the cell nucleus. The nucleus is the cell’s control room, where most of the DNA is stored. It’s wrapped in a thin nuclear envelope, like a flexible shell.

The team found this pattern in melanoma and also in breast and prostate cancers. When cholesterol levels in the nuclear envelope were high, the nucleus became easier to deform. In other words, it became more squishy. This is important because cancer cells often have to squeeze through tight gaps between other cells to spread. A squishier nucleus makes that squeezing easier, so the cancer can invade new tissues more successfully.

High cholesterol did something else, too: it made the nuclear envelope more fragile. Fragile envelopes were more likely to tear in small, local spots. When a tear happens, the DNA inside can be exposed to forces that damage it. Damaged DNA can lead to new mutations, and some of those new mutations can make the cancer even more aggressive.