Collective invasion in breast cancer requires a conserved basal epithelial program

Kevin J. Cheung, Edward Gabrielson, Zena Werb, and Andrew J. Ewald,

Cell (2013) 155, 1639–1651

Speaker: Hsin-I Wang (汪欣儀)                           Time: 14:00~15:00, April 23, 2014

Commentator: Dr. Yao Chang (張堯 博士) Place: Room 601

Abstract :

Nowadays, cancer is a large group of diseases overall the world. Among these cases, breast cancer accounts for 22.9%, even more, of all cancers in women. There are about 0.5 million breast cancer patients dead each year. Metastasis is the most threatens cause of death for breast cancer patients. Invasion is a fundamental step in tumor progression and a driving force for metastasis. Clinically, the transition from in situ to invasive breast cancer correlates with a strong reduction in overall survival (1). Carcinomas typically invade as a cohesive multi-cellular unit, a process termed collective invasion. When metastasis occurs, single cells on the edge of a tumor, termed leader cells, act as guides to leave the tumor nest, with many tumor cells following behind. A central problem in collective invasion is how a group of adherent epithelial cancer cells acquires motile invasive behavior (2). The authors found that those leader cells expressed cytokeratin14 (K14), which can regulate different cellular processes like apoptosis, cell transformation, cell migration and cell differentiation (3). K14 helps the formation of cytoskeleton of many cell types, giving them structure and helping them to move. K14 was present in almost all leader cells but was very rare in the noninvasive parts of the tumor. The more invasive a tumor was, the more cells with K14 it had. The authors obtained breast tumors from MMTV-PyMT mice and injected tumor cells without K14 into another mice. They found that the new tumors showed smooth borders, with essentially no invasions occurring. They also noted that those tumor cells require K14 to lead the invasion, and the tumor cells need only some leader cells to start the process of metastasis. The results suggest that targeting a basal invasive program expressed in a minority of tumor cells is sufficient to disrupt the invasive process in an advanced carcinoma.

References :

1.      Polyak K. Molecular markers for the diagnosis and management of ductal carcinoma in situ. J. Natl. Cancer. Inst. Monogr. 41, 210-213 (2010).

2.     Ryan S. Gray, Kevin J. Cheung, and Andrew J. Ewald. Cellular mechanisms regulating epithelial morphogenesis and cancer invasion. Curr. Opin. Cell Biol. 22, 640-650 (2010).

3.     Xiaoou Pan, Ryan P. Hobbs, and Pierre A. Coulombe. The expanding significance of keratin intermediate filaments in normal and diseased epithelia. Curr. Opin. Cell Biol. 25, 47-56 (2013).