INTEGRIN TRAP: Rab25 proteins bind integrins in the cell membrane and shuttle them to lysosomes. If the Rab25 shuttles the integrins to a lysosome where CLIC3 is absent, then they are degraded (A). If CLIC3 is present on the surface of the lysosome, the integrins survive and are shuttled to the rear of the cell where they help the cell detach from the extracellular matrix (ECM) and become metastatic (B). PRECISION GRAPHICS
Rab25 has perplexed cancer researchers for years. The small membrane-trafficking enzyme sometimes appears to drive cancer and at other times to protect against it: it is associated with aggression in breast and ovarian cancer and with suppression of intestinal tumors. Intrigued by this contradiction, Jim Norman and colleagues at the Beatson Institute for Cancer Research in Glasgow screened Rab25-expressing cells for additional proteins that might be involved in its function.
That screen showed that chloride intracellular channel protein 3 (CLIC3) was the most significantly upregulated gene in cultured Rab25-expressing cells. Using biochemical approaches, the team found that both Rab25 and CLIC3 control the intracellular transport of integrins—transmembrane proteins that attach a cell’s cytoskeleton to the extracellular matrix (ECM) and send signals between the two. Integrins ...
