Loss of Fam38 gets SCLC moving

Small cell lung cancer (SCLC) is a very aggressive form of lung cancer; response of patients to the initial chemotherapy is good, however in most cases the cancer reoccurs and progresses. A key step in progression of advanced cancer is the breaking away of a number of cells from the original tumour which move through the body and act as a seed for new tumours in areas such as the lymph nodes. This process, termed metastasis requires cells of the original tumour to take up a more invasive pattern of cell movement. The way in which cells move is a complicated and highly regulated process, cancers hijack this processes to their own end: metastasis. 

The majority of solid tumours rely on a combination of proteins called integrins, which regulate how well one cell sticks to other cells at it moves across them, and a group of enzymes which break up and remodel the environment surrounding the tumour. However, a recent study by McHugh et al. from Edinburgh MRC and Kings College London has shown that SCLC can adopt a vastly different method of cell movement.

Normal lung cells express high levels of a protein called Fam38, this protein is involved in integrin regulation for cellular movement. A key initial observation by the group was that SCLC cells, in contrast, have very low levels of Fam38. In normal lung cells McHugh and colleagues artificially reduced Fam38 levels to a similar degree as seen in SCLC cells and looked to see what changes Fam38 loss caused. These cells showed a remarkable loss of dependence on integrins for their movement and consequently were less able to stick to other cells. 

Cells lacking Fam38 adopted a different method of movement which allowed them to move faster over a two-dimensional area and further through a three-dimensional tissue-like substance. This increased invasiveness following Fam38 loss may explain why, in part, SCLC is so aggressive and difficult to treat.

Drug discovery for treatment of the most common form of lung cancer, non-small cell lung cancer (NSCLC), has advanced quicker than for SCLC. With the discovery of the role of Fam38 in SCLC a potential new therapeutic target has been found. Further research is required, but watch this space!

Mentioned Articles:

McHugh BJ, 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): e40346. doi:10.1371/journal.pone.0040346