Issues

It is estimated that more than 200,000 new cases of lung cancer will be diagnosed this year. Studies seek to understand the events involved in malignant transformation, which include the identification of molecular and genetic events that drive the progression from normal to at-risk epithelium to invasive cancer. Although metastatic behavior is considered to occur post-transformation, clinical findings suggest the metastatic process is also operative in early disease pathogenesis, particularly in the context of epithelial-mesenchymal transition. Pagano et al (page 514) describe a subpopulation of highly motile human bronchial epithelial cells isolated from a model of lung premalignancy. The cover image shows this subpopulation stained for filamentous actin and highlights large lamellipodia and actin arcs, structures associated with cell movement and largely absent in the parent population. The study shows this subpopulation operates in a Rac1-dependent manner and has enhanced metastatic properties in a murine metastasis model. Understanding, targeting and preventing critical molecular and biophysical mechanisms associated with enhanced motility may provide a new therapeutic approach to prevent metastases in early stage lung cancer.