Leading the Invasion

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Science  03 Jan 2014:
Vol. 343, Issue 6166, pp. 8
DOI: 10.1126/science.343.6166.8-a
CREDIT: K. J. CHEUNG ET AL., CELL 155, 1639 (12 DECEMBER 2013) © 2013 ELSEVIER INC.

Metastasis of solid tumors requires that normally immotile epithelial cancer cells acquire the ability to invade surrounding tissue. Current models depict invasion as a multicellular event dependent on the collective action of stromal cells and specialized, but poorly defined, subpopulations of cancer epithelial cells. Identifying the distinguishing molecular features of the most invasive cells could potentially provide new targets for therapeutic intervention.

Studying breast cancer invasion in vitro, in mouse models, and in human tumor samples, Cheung et al. found that the cancer cells “leading” the invasion expressed genes characteristic of basal epithelium, including cytokeratin-14 (K14) and p63. The leader phenotype appeared to be a differentiation state rather than a fixed lineage, as K14-negative luminal cells (a mammary epithelial cell type that gives rise to most breast cancers) were found to undergo conversion to invasive behavior in vitro, concomitant with the acquisition of K14 expression. Notably, shRNA-mediated inhibition of K14 or p63 expression blocked the invasive capacity of breast tumors in vitro, suggesting that therapies aimed at disrupting the basal epithelial program might impede metastasis.

Cell 155, 1639 (2013).

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