Cancer Spread Takes More Than a Twist of Fate

Cancer researchers have found that in order to metastasize, cancer cells must activate the gene that codes for the gene regulatory protein Twist. Cancer cells lacking Twist can grow, but they cannot migrate to establish new tumors in distant tissues.

Investigators at the Whitehead Institute for Biomedical Research (Cambridge, MA, USA) used microarray technology to examine patterns of gene activation in metastatic and nonmetastatic cancer cells taken from mouse tumors. They reported in the June 25, 2004, issue of Cell that Twist, a gene regulator normally active in the developing embryo, was functioning in the metastatic cells but not in the nonmetastatic cells.

Further studies revealed that if the Twist gene was inactivated in a normally metastatic tumor, it failed to metastasize after being injected into naïve mice. Twist expression resulted in loss of E-cadherin-mediated cell-cell adhesion, activation of mesenchymal markers, and induction of cell motility. Lacking these influences, Twist-deficient cancers could grow but not spread.

Despite its obvious importance in the process of metastasis, Twist is not the whole story. Senior author Dr. Robert Weinberg, professor of biology at the Massachusetts Institute of Technology (Boston, MA, USA) said, "There are a number of other regulatory proteins that have been studied in other labs and have properties very similar to those of Twist. The other regulators undoubtedly will play important roles in other types of human metastatic cancer.”





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Whitehead Institute for Biomedical Research