Metabolic signal curbs cancer-cell migration

Metabolic signal curbs cancer-cell migration 02.07.2019

Metabolic signal curbs cancer-cell migration

Cancer becomes lethal when tumour cells spread from their primary site in the body to invade distant organs — a process termed metastasis. For this complex event to occur, the cells must invade their surrounding tissue, enter the bloodstream and colonize another location, where secondary tumours called metastases form. Several of the early steps in metastasis, including cell migration, can be induced by the abnormal activation of a normal developmental program called epithelial–mesenchymal transition (EMT), in which the epithelial cells that line body surfaces take on the characteristics of mesenchymal cells, which have migratory properties. Writing in Nature, Wang et al. identify a previously unknown mechanism by which a molecule generated in cellular metabolism inhibits the induction of EMT and thereby restrains the metastasis of lung cancer in mice.

The molecules formed during metabolism can have a key role in supporting the survival, proliferation and metastasis of tumour cells. Cancer cells have a higher than normal level of nutrient uptake and altered metabolic pathways, and these properties ensure that tumours make the metabolites they need to grow. When tumour cells migrate into the bloodstream, they experience cellular stress. This is characterized by an increase in molecules called reactive oxygen species, and metabolic alterations that counter such stress can promote metastasis. But whether metabolic pathways affect other aspects of metastasis has been poorly understood.

To investigate this further, Wang and colleagues individually blocked the expression of 111 metabolic enzymes in human lung cancer cells that had arisen from epithelial cells. Using these cells grown in vitro, the authors found that inhibiting production of the enzyme UGDH impaired the migratory capacity of the cells. UGDH converts UDP-glucose (UDP-Glc) to UDP-glucuronic acid (UDP-GlcUA), which is needed to make polysaccharide molecules such as hyaluronic acid, a component of the extracellular matrix material in the tissues in which epithelial cells reside. Hyaluronic acid can activate receptors on the surface of cells to initiate EMT, and its accumulation in tumours is often associated with poor clinical outcome.


Back to the list