Epigenetically distinct sister chromatids and asymmetric generation of tumor initiating cells

Cancer stem cells (CSC) are thought to be an important source of cancer cells in tumors of different origins. Mounting evidence suggests they are generated reversibly from existing cancer cells, and supply new cancer cells during tumor progression and following therapy. Elegant lineage mapping stud(ies are identifying progenitors, and in some cases differentiated cells, as targets of transformation in a variety of tumors. Recent evidence suggests resulting tumor initiating cells (TIC) might be distinct from CSC. Molecular pathways leading from cells of tumor origin to precancerous lesions and cancer cells are only beginning to be unraveled. We review a pathway where asymmetric division of precancerous cells generates TIC in a K-Ras-initiated model of lung cancer. And, we compare unexpected steps in this asymmetric division to those evident in well-studied stem cell models.