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2 proteins compete for 1 port on a growth factor; 1 promotes metastasis, the other blocks it
Date:1/23/2014

ood that the cancer will spread and guide treatment decisions.

For example, an analysis of an ovarian cancer patient's initial presentation could indicate early whether chemotherapy will be needed in addition to surgery to combat metastasis. Ovarian cancer patients with low Grb2 expression levels could have an increased risk that their cancer will spread.

Trade-off matters in at least 5 cancer types

Analysis of published data on 20 cancer cell lines including lung, ovarian, kidney, breast and colon cancers, showed that a cancer's metastatic potential is linked to the relative concentration of Plcγ1 and Grb2 expression. Overexpression of Plcγ1 and low expression of Grb2 resulted in a high likelihood of metastasis, while high Grb2 and low Plcγ1 indicated a low likelihood that the cancer will spread.

Ladbury and colleagues set out to explain this relationship and its apparent effect with a series of cell line experiments that showed:

  • Grb2 blocks the binding of Plcγ1 to FGFR2.
  • Both proteins connect with the same site on FGFR2, using a similar domain on each protein to connect to the growth factor receptor.
  • Binding to FGFR2 activates Plcγ1.
  • Overexpression of Plcγ1 leads to increased invasion of other tissues, a vital step in metastasis.

All of this action occurs in the cell's stable state, or homeostasis, before a growth factor stimulates FGFR2 into action, which is what made the team's 2012 finding so striking. The domain (SH3) that each protein uses to connect to FGFR2 is not used in normal signaling.

FGFR2 spans a cell's outer membrane, with its outer portion receiving growth factors and its inner region passing along activating signals that order other proteins to perform their functions. In this case, there's no active signaling in the usual sense, Ladbury said.

Crucial events occur in background activity of cells


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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

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