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TurretLauncher OP t1_iqlc1th wrote

Abstract

We identify the sodium leak channel non-selective protein (NALCN) as a key regulator of cancer metastasis and nonmalignant cell dissemination. Among 10,022 human cancers, NALCN loss-of-function mutations were enriched in gastric and colorectal cancers. Deletion of Nalcn from gastric, intestinal or pancreatic adenocarcinomas in mice did not alter tumor incidence, but markedly increased the number of circulating tumor cells (CTCs) and metastases. Treatment of these mice with gadolinium-a NALCN channel blocker-similarly increased CTCs and metastases. Deletion of Nalcn from mice that lacked oncogenic mutations and never developed cancer caused shedding of epithelial cells into the blood at levels equivalent to those seen in tumor-bearing animals. These cells trafficked to distant organs to form normal structures including lung epithelium, and kidney glomeruli and tubules. Thus, NALCN regulates cell shedding from solid tissues independent of cancer, divorcing this process from tumorigenesis and unmasking a potential new target for antimetastatic therapies.

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TurretLauncher OP t1_iqlcbfk wrote

Potential cancer breakthrough as scientists finally discover how tumours 'hijack' healthy cells to spread around the body

Scientists have discovered that cancer cells ‘hijack’ a process used by healthy cells to spread around the body, completely changing current ways of thinking about cancer.

Despite being one of the main causes of death in cancer patients, metastasis — when cancer spreads — has remained incredibly difficult to prevent.

This is largely because researchers have found it hard to identify key drivers of this process, which could be targeted by drugs.

Now, they have discovered a protein called NALCN may play a key role.

In experiments in mice, they found that blocking the activity of the NALCN protein triggered metastasis.

They also discovered that when they removed the protein from mice without cancer, this caused their healthy cells to leave their original tissue and travel around the body where they joined other organs.

This suggests that metastasis isn’t an abnormal process limited to cancer as previously thought, but is a normal process used by healthy cells that has been exploited by cancers to migrate to other parts of the body.

NALCN stands for sodium (Na+) leak channel, non-selective. Sodium leak channels are expressed predominately in the central nervous system but are also found throughout the rest of the body.

These channels sit across the membranes of cells and control the amount of salt that goes in and out of the cell.

However, it is not yet clear why these channels seem to be implicated so directly in cancer metastasis.

Lead researcher on the study and senior research associate at the Cancer Research UK Cambridge Institute, Dr Eric Rahrmann, said: ‘We are incredibly excited to have identified a single protein that regulates not only how cancer spreads through the body, independent of tumour growth, but also normal tissue cell shedding and repair.

‘We are developing a clearer picture on the processes that govern how cancer cells spread.

'We can now consider whether there are likely existing drugs which could be repurposed to prevent this mechanism from triggering cancer spreading in patients.’

The findings were published in the journal Nature Genetics.

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