Scientists from University of Manchester have demonstrated that how proteins were cut in lung cancer cells, making metastasis possible. Their finding may be helpful in the development of cancer therapy to block metastasis in the future. This study was published in Cell Reports.

Metastasis, a multistep process beginning with local invasion and culminating in the colonization of distant organs by cancer cells, is responsible for more than 90% of all cancer deaths. Metastasis of arcinoma cells often commences with the disassembly of junctional complexes and downregulation of other epithelial traits coupled with the acquisition of migratory and invasive mesenchymal phenotype(epithelial-mesenchymal thransition[EMT]).

In this study, researchers show that in response to human grow factor(HGF), HUWE1(WWE domain-containing protein 1) ubiquitylates TIAM1(metastasis inducing protein 1) on lysine 595, triggering its proteasomal degradation predominantly at cell-cell adhesions, thereby enabling disassembly of cell junctions and induction of cell migration and invasion, including in lung carcinoma cells. They also show that TIAM1 and HUWE1 protein levels are negatively correlat3ed in early-stage lung cancer specimens, consistent with this regulatory mechanism operating in human tumors.

Reference:

Vaughan L, Tan C T, Chapman A, et al. HUWE1 Ubiquitylates and Degrades the RAC Activator TIAM1 Promoting Cell-Cell Adhesion Disassembly, Migration, and Invasion[J]. Cell Reports, 2014.