Using a molecular cellular compass, individual cells in complex organisms know which way is up or down, in epithelial cells known as apical-basal polarity. Determining the orientation is essential for an individual cell to perform it’s designated tasks.

Now it appears that the same compass also defines the direction of cells when migrating by establishing a morphological back and a front. These are the conclusions of a recent study lead by scientists Michiel Pegtel and John Collard from the Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital (NKI-AVL) in the Netherlands published in the October 9th issue of the scientific journal Current Biology.

Many cell types acquire asymmetry for their biological function. Yeast cells, worms, mice and men all use the same cellular compass, made up of a combination of protein complexes that is essential for the spatial orientation of the cell. The Par-Tiam1 polarity complex is a crucial component of the compass. Tiam1 was earlier identified as a gene that could influence dissemination of tumour cells.

Skin cells from a mouse with an intact compass. Using a flat protrusion at the front the cells move in straight line.

In a previous study by the group of John Collard from the NKI-AVL, it became clear that the Par-Tiam1 complex is crucial for top/bottom orientation of adherent cells. This form of cell asymmetry is required for the cells to properly adhere and to form a tightly connected cellular structure. However, loss of orientation or cell polarity leads dissociation of cell-cell contacts and in tumours to dissemination of cancer cells.

Now it appears that the Par-Tiam1 complex also controls front-rear orientation of the cell. This way cells that leave their brethrens behind after detaching know how to find their way while migrating. Collard and colleagues showed that mouse skin cells with a functional compass migrate in a straight linear fashion toward their target. The cells persistently move forward like a caterpillar, continuously expanding and retracting in one direction. But when the Par-Tiam1 complex is disrupted or shut-down, the cells migrate aimlessly in random direction.

Pegtel & Collard: “It is becoming clear that polarity of cells is crucial for embryonic development and function of many biological processes in humans and lower organisms alike. It guides immune cells to sites of infection and directs the organization of the neuronal network. But at the same time, it also prevents detachment of adherent cells; we were very surprised that one protein complex regulates such seemingly opposing tasks”. This could explain the findings that Tiam1 is able both to promote and prevent metastasis in different tumours.

Article: The Par-Tiam1 Complex Controls Persistent Migration by Stabilizing Microtubule-Dependent Front-Rear Polarity, D. Michiel Pegtel, Saskia I.J. Ellenbroek, Alexander E.E. Mertens, Rob A. van der Kammen, Johan de Rooij, and John G. Collard, Current Biology, Vol 17, 1623-1634, 09 October 2007