Refining the role for adult stem cells as cancer cells of origin

•Adult stem cells are often cancer cells of origin for epithelial cancers.•The cancer cell of origin can be altered by cell intrinsic influences, such as the mutational landscape and cell cycle state.•The cancer cell of origin can be altered by cell extrinsic influences, such as inflammation and abnormal stromal signaling.

Significant progress has been made to identify the cells at the foundation of tumorigenesis, the cancer cell of origin (CCO). The majority of data points towards resident adult stem cells (ASCs) or primitive progenitors as the CCO for those cancers studied, highlighting the importance of stem cells not only as propagators but also as initiators of cancer. Recent data suggest tumor initiation at the CCOs can be regulated through both intrinsic and extrinsic signals and that the identity of the CCOs and their propensity to initiate tumorigenesis is context dependent. In this review, we summarize some of the recent findings regarding CCOs and solid tumor initiation and highlight its relation with bona fide human cancer.