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Histopathologic image of small cell carcinoma of the lung. CT-guided core needle biopsy. (Image credit: Wikipedia)A team of researchers in the UK have discovered how the absence of a single gene makes it easier for tumour cells to migrate more freely in lung cancer patients. More people suffer  — and die — from lung cancer than any other kind.  Small cell lung cancer (SCLC) is an extremely aggressive form of lung cancer thanks to its tendency to metastasise quickly, spreading to other organs early. In order to migrate, metastasising tumour cells have to break free of the extracellular matrix (ECM), the network of material around our cells which supports them and binds them to each other. That’s where this particular gene, Fam38A, comes into the story.

Cells are normally anchored to the ECM by a group of proteins on their surface called integrins. Integrins are made up of several different subunits, one of which is activated by Fam38A. In an earlier study, the researchers produced cells with an artificially reduced level of Fam38A; these cells had less integrin activity, making them less adhesive than usual. Since cells from the lungs of SCLC patients have lower levels of Fam38A, the researchers wondered whether the loss of Fam38A somehow enabled cancerous cells to move about more freely.

Although it might seem like being unbound would make cells free to travel, some types of cells actually need integrins in order to move; they use the adhesion between the integrins and the ECM to gain traction and pull themselves along. Cells which aren’t anchored properly usually can’t move around; they also can’t divide, which is part of the body’s defense against cancerous growths.  Tumour cells can overcome this limitation, though.  They switch to another kind of motion and travel like an amoeba, using their cellular skeleton to push themselves through the surrounding material. When the team compared the movement of normal cells and low-Fam38A cells with a microscope, they found that the low-Fam38A cells moved about much more freely than the normal cells, migrating an average of four times further, and were able to push their way about twice as far into a gel. These cells were also more round, as well as having a rearranged cellular skeleton and other characteristics associated with amoeba-like movement.

Fam38A-migrations

Tracings of the movement of normal cells (left) and low-Fam38A cells (right).

Fam38A cells

Microscope images of normal cells (left) and cells with reduced levels of Fam38A (right). The cellular skeleton is shown in green and a marker of amoeboid migration is shown in red. The blue oval is the nucleus.

The authors write that “a Fam38A-independent form of migration could cause a fundamentally important […] change with drastic consequences for lung cancer cell metastasis” and suggest that Fam38A could be used as “an important biomarker for increased metastasis in SCLC tumours.” Researchers in the US independently found a link between Fam38A and cancer, though in that case increased levels of Fam38A were associated with breast cancer.  These discoveries will doubtless prove useful, but they shouldn’t be oversold. People are understandably eager for breakthroughs, particularly in areas like cancer research, and discoveries are often over-hyped or under-reported accordingly. There’s more to science than breakthroughs, though; it’s usually a steady stream of research that happens between those dramatic moments. We learn about our bodies and the world around us from the slow accumulation of knowledge by careful, methodical work, which is the heart of good science and the foundation of every discovery — from simple ornaments on the tree of knowledge to surprising breakthroughs that reshape our view of the world.

Ref
McHugh, B., Murdoch, A., Haslett, C., & Sethi, T. (2012). Loss of the Integrin-Activating Transmembrane Protein Fam38A (Piezo1) Promotes a Switch to a Reduced Integrin-Dependent Mode of Cell Migration PLoS ONE, 7 (7) DOI: 10.1371/journal.pone.0040346
(The PLoS journals are all open access, which means the paper is freely available to everyone.)

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