When cancer cells can't let go

April 13, 2009
The invadopodia (glowing dots) speckling a cell lacking FAK (left) are rare on a control cell (right). Credit: Chan, K.T., et al. 2009. J. Cell Biol. doi:10.1083/jcb.200809110.

Like a climber scaling a rock face, a migrating cancer cell has to keep a tight grip on the surface but also let go at the right moment to move ahead. Chan et al. reveal that the focal adhesion kinase (FAK) coordinates these processes to permit forward movement. The study will be published online April 13 and will appear in the April 20 print issue of the Journal of Cell Biology.

Crawling send out extensions called invadopodia. By releasing enzymes that dissolve the extracellular matrix (ECM), invadopodia clear a path for the cell to wriggle through. As they move, cancer cells get traction by temporarily attaching to the ECM through focal adhesions. FAK spurs focal adhesions to disengage, and it is more abundant in metastatic tumors. Whether FAK also regulates invadopodia was unknown.

When Chan et al. removed FAK, cells were much less invasive. But to the team's surprise, the FAK-lacking cells sprouted extra invadopodia. The cells also sported large focal adhesions that were particularly sticky. The protein Src serves as FAK's helper. FAK and Src work together to phosphorylate tyrosines in proteins such as paxillin, which then disassemble the focal adhesion. But the team found that in cells missing FAK, the phosphorylated proteins accumulated in invadopodia. Src's localization reflects this difference. In control cells, Src accumulated in focal adhesions. In FAK's absence, Src headed to the invadopodia.

The work suggests that FAK controls movement by balancing the number of invadopodia that create a path for migration and the number of focal adhesions that hold the cell back. The next question, the researchers say, is how FAK and Src integrate these events to promote invasion.

More information: Chan, K.T., et al. 2009. J. Cell Biol. doi:10.1083/jcb.200809110. www.jcb.org

Source: Rockefeller University (news : web)

Related Stories

Recommended for you

Alternative splicing, an important mechanism for cancer

September 22, 2017
Cancer, which is one of the leading causes of death worldwide, arises from the disruption of essential mechanisms of the normal cell life cycle, such as replication control, DNA repair and cell death. Thanks to the advances ...

'Labyrinth' chip could help monitor aggressive cancer stem cells

September 21, 2017
Inspired by the Labyrinth of Greek mythology, a new chip etched with fluid channels sends blood samples through a hydrodynamic maze to separate out rare circulating cancer cells into a relatively clean stream for analysis. ...

Drug combination may improve impact of immunotherapy in head and neck cancer

September 21, 2017
Checkpoint inhibitor-based immunotherapy has been shown to be very effective in recurrent and metastatic head and neck cancer but only in a minority of patients. University of California San Diego School of Medicine researchers ...

Whole food diet may help prevent colon cancer, other chronic conditions

September 21, 2017
A diet that includes plenty of colorful vegetables and fruits may contain compounds that can stop colon cancer and inflammatory bowel diseases in pigs, according to an international team of researchers. Understanding how ...

New kinase detection method helps identify targets for developing cancer drugs

September 21, 2017
Purdue University researchers have developed a high-throughput method for matching kinases to the proteins they phosphorylate, speeding the ability to identify multiple potential cancer drug targets.

Brain cancer growth halted by absence of protein, study finds

September 20, 2017
The growth of certain aggressive brain tumors can be halted by cutting off their access to a signaling molecule produced by the brain's nerve cells, according to a new study by researchers at the Stanford University School ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.