What controls cell shape?

16 December 2013

Interview with

Helen Matthews, University College London

Fat cells in adipose tissueHelen - In the human body, cells are all kinds of different shapes and it reflects that specialist nature of different types of cells.  So, you can imagine that for example, a neuron that has to carry electrical signal from your foot, all the way to your spine has to be very long and thin, whereas another type of cell like a red blood cell is small and round because it's perfectly suited to carry oxygen.

Simon -   What's controlling the shape of the cell?

Helen -   So, cells are actually very good at controlling their own shape and they do this using specialised proteins which are called the cytoskeleton which is like a scaffolding inside the cell which gives it its specific shape.

Simon -   What aspect of shape are you looking at?

Helen -   So, I'm studying how cell shape actually changes during cancer.  A lot of cells in the body are in epithelium which are these very tightly controlled layers of square-shaped cells.  What you nearly always find in cancer is that the cells lose this nice regular shape and become kind of all kinds of different shapes.  This helps the cancer cells do many different things for example to spread through the body by invading other tissues.  They become very long and thin and invasive structures rather than keeping their nice regulated square shape.  One of the other things that I'm studying in particular about cancer cells is how they also change shape when they divide.

Simon -  So, what does happen to cell shape during division?

Helen -   So, when cells divide, they lose their square shape and they become spherical.  We think that this is really important to help cells divide accurately in two.  It's much easier to segment a sphere into two equal parts than an odd-shaped or an uneven-shaped cell.

Simon -   I presume that becoming spherical makes the cell bigger and actually allows it to take up the space around it and that that would be an advantage when you're trying a tumour.

Helen -   Yeah, exactly.  So, we think that actually this is something that happens normally in all the cell types when they divide, but actually, the cancer cells are able to exploit this and swell up even more so that they're able to divide efficiently in a tumour.

Simon -   How are you looking into the role of shape in cancer?

Helen -   I spend a lot of time looking down the microscope at cells dividing and looking at the shape changes that happen to them.  I've got a video here where you can see the cell rounding up as it divides.

Simon -   Wow!  So, I'm looking at a single cell side on and the cell suddenly lifts up and it becomes completely spherical.  In the middle of the cell, I'm assuming this is the genetic material inside the cell.  It's dividing as the sphere divides into two.  So, it's quite a dramatic shape change from a flat cell to a spherical cell and then back down into two flat cells.

Helen -   Yeah, exactly.  The cell essentially goes from being the shape of like a fried egg to a tennis ball, and it increases in height a lot.  So, you see that the cells are very flat and then it really increases its height.

Simon -   Now, I suppose in a tumour, it wouldn't be flat on a slide in a microscope.  How does this work inside a tumour?

Helen -   We believe that actually, in a tumour, a cell would swell up to become spherical in the same way, but this would allow it to have space to be able to divide in two.

Simon -   So, that's what you are showing me here.  This looks a bit like a cell sandwich.  We've got a cell on a flat surface.  We've got almost like a gel on top.  What's going on here?

Helen -   So, what they did was, they put this on a really small space.  They squashed it under a gel and if you use a really soft gel, then the cells are able to round up and divide normally.  But if you use a really hard gel then the cell is no longer able to generate enough force to round up and you get these cells dividing when they're still flat.  In cancer cells, what they found is that actually, this is disastrous and the cell really fails division and is unable to divide properly, unless it's able to do this cell shape change.

Simon -   How are you looking at what underlies this genetically?

Helen -   So, I really want to find out which genes are involved in this shape change that happens when cells divide.  To do this, I used a method called an RNAi screen where what we do is we systematically knockdown different genes, turn them off, to see which have an effect on cell shape during division.

Simon -   Did you have in mind which genes to target in the first place.

Helen -   Yes, because obviously, there's a great many genes in the human genome and it would be a big undertaking to knock them all down.

Simon -   I guess that would take quite a long time.

Helen -   Exactly and a lot of money.  So, we specifically chose genes that we already knew are activated when cells divide because we thought that if they're active then they could be good candidates to be involved in changing the cell shape.

Simon -   What did you find?

Helen -   We've identified one gene that really has a strong effect on cell shape and division.  It's a gene called Ect2.  It's a molecular switch, so it's actually a master switch within the cell that controls the cell cytoskeleton.  It's involved in building up the scaffolding that gives the cells their shape.  This has a very profound effect on cell shape because if you remove Ect2 from the cell, they no longer round up and they stay completely flat when they divide.

Simon -   So, what's the difference between a cancer cell and a non-cancer cell?

Helen -   So, that's what actually we're really trying to find out now.  Why is it that cancer cells behave differently in these shape changes at division compared to non-cancer cells?  To do this, we're taking non-cancer normal human cells and activating genes that are frequently activated in cancer.

Simon -   So, you're almost making a non-cancer cell pretend that it's cancer.

Helen -   Exactly.  In fact, we're transforming it into a cancer cell then we're studying what happens to the cytoskeleton and to the shape of the cell when it divides.

Simon -   And what happens?

Helen - I don't know yet.  This is what I'm studying at the moment.

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