How Invading cancer cells affects and deploys fuel to the front line

How Invading cancer cells affects and deploys fuel to the front line ...

Invading armies require constant supply of energy and armaments. This is particularly true when invaders are cells, such as when tumor cells break away from their neighbors and spread to other parts of the body in a process called metastasis -- the most deadly part of cancer.

The tiny wormC.elegans, created by a Duke University student, provides a new insight into how invading cells amass and deploy fuel to the front lines of invasion to power their cellular break-through devices.

Two glucose transporters, which were deactivated, disrupt the energy supply to invadingworm cells, and even keep some of them in their tracks, have been identified in a study published in the journalDevelopmental Cell.

Thefindingscould will eventually lead to fresh avenues to narrow supply lines that allow cancer cells to seize in humans.

This is a big deal because it offers us a new dimension of invasive cells to target therapeutically, according to Sherwood.

Metastatic cancer is notoriously difficult to treat. Most cancer medications work by destroying tumor cells or slowing their growth. However, quite a few of the over 200 anti-cancer medications that have been approved for clinical use effective prevent cancer from departing from the original tumor and spreading to other organs, the cause of the vast majority of cancer-related deaths.

According to Sherwood, the author of the paper, we have no therapies to accomplish this objective. It''s ironic, because it''s the most deadly aspect of cancer, but it''s the one that we can understand the most.

The reason for this change is that the process has been difficult to understand. Cancers are unpredictable, and most cancer cells meetastasize deep inside the body, beyond the reach of light microscopes.

Sherwood said there is no way to distinguish an infected cell in the act.

So sherwoods'' laboratory investigates a similar approach in millimeter-long transparent worms calledC. elegans. Before a developing worm can finish building its reproductive tract, a specialist cell called the anchor cell must break through a dense, sheet-like mesh that separates the worms uterus from its vulva to clear a path for mating and laying eggs.

Both worm cells and human cancer cells are using the same invasive machinery, a slew of piston-like projections that sprout from the cell surface and spread across tissue barriers to clear a path for cells to pass through, like punching out an escape tunnel.

The question is, what''s being used to keep these machines? According to Duke''s first authorAastha Garde, who is a PhD student in cell biology. How can we impose that on the machines itself, so they don''t waste energy?

The researchers combined a cellphone connected to a powerful microscope to look inside tiny worm cells hundreds of times smaller than a grain of salt and observe their break-ins in action.

As the cell approached to break through, a burst of light appeared behind the cells front lines, revealing an outpouring of ATP during the breach.

The ATP is produced by organelles namens mitochondria, the cell''s energy factories, that are guided to the cells'' front lines of invasion by a molecular cue called netrin, according to researchers.

The researchers studied an estimated 8,300 of the worms, sifting them one by one, using a technique called RNA interference to determine if the worm cells were still able to break through.

They identified two genes that encode gate-like proteins called FGT-1 and FGT-2. These build up along the cells borders just before invasion and allow more glucose into the cell, where it is broken down to produce ATP.

The researchers deactivated these genes, but glucose and ATP levels remained unchanged, and worm cells were forced to spread. Through the microscope, they saw cells making a costly effort to put out new piston-like projections, to push through, but most were delayed, and a third of the cells remained unchanged.

According to Garde, without glucose, basically the entire apparatus that the anchor cell uses to bust through the basement membrane is affected.

Researchers hope their research on worms will aid them to discover the Achilles heel of cell invasion, according to Sherwood.

Sherwood said this is an aspect of how cell invasion has been overlooked. If we can stop this burst of ATP, we may limit or stop cell invasion.

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