Gene that stops spread of common lung cancer identified

Written by PTI | Washington | Updated: Jul 18 2014, 23:27pm hrs
Lung canacerCancer can switch on and off molecular anchors protruding from the cell membrane.(Thinkstock)
A gene responsible for stopping the movement of cancer from the lungs to other parts of the body has been identified by scientists.

By identifying the cause of this metastasis - which often happens quickly in lung cancer and results in a bleak survival rate - scientists at the Salk Institute for Biological Studies in the US are able to explain why some tumours are more prone to spreading than others.

To become mobile, cancer cells override cellular machinery that typically keeps cells rooted within their respective locations.

Cancer can switch on and off molecular anchors protruding from the cell membrane (called focal adhesion complexes), preparing the cell for migration.

This allows cancer cells to begin the processes to traverse the body through the bloodstream and take up residence in new organs.

In addition to different cancers being able to manipulate these anchors, it was also known that about a fifth of lung cancer cases are missing an anti-cancer gene called LKB1 (also known as STK11).

Cancers missing LKB1 are often aggressive, rapidly spreading through the body. However, no one knew how LKB1 and focal adhesions were connected.

Now, the Salk team has found the connection and a new target for therapy: a little-known gene called DIXDC1. The researchers discovered that DIXDC1 receives instructions from LKB1 to go to focal adhesions and change their size and number.

When DIXDC1 is "turned on," half a dozen or so focal adhesions grow large and sticky, anchoring cells to their spot.

When DIXDC1 is blocked or inactivated, focal adhesions become small and numerous, resulting in hundreds of small "hands" that pull the cell forward in response to extracellular cues.

That increased tendency to be mobile aids in the escape from, for example, the lungs and allows tumour cells to survive travel through the bloodstream and dock at organs throughout the body.

"The communication between LKB1 and DIXDC1 is responsible for a 'stay-put' signal in cells. DIXDC1, which no one knew much about, turns out to be inhibited in cancer and metastasis," said first author and PhD graduate student Jonathan Goodwin.

Researchers have found two ways to turn off this "stay-put" signal. One is by inhibiting DIXDC1 directly. The other way is by deleting LKB1, which then never sends the signal to DIXDC1 to move to the focal adhesions to anchor the cell.

In further experiments researchers took metastatic cells, which had low levels of DIXDC1, and overexpressed the gene. The addition of DIXDC1 did indeed blunt the ability of these cells to be metastatic in vitro and in vivo.

The new study is published in the journal Molecular Cell.