title: How does multistep tumorigenesis really proceed?
abstract: Identifying the cancer cells-of-origin is of great interest, as it holds the potential to elucidate biologic mechanisms inherent in the normal cell state that have been co-opted to drive the oncogenic cell state. An emerging concept, proposed here, states that cancer stem cells, key players in cancer initiation and metastasis, arise when transit-amplifying cells with mutant genomes dedifferentiate and enter the stem cell state. This model contrasts with the notion that cancer stem cells are the direct products of neoplastically transformed normal tissue stem cells.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Chaffer
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts. Ludwig MIT Center for Molecular Oncology, Cambridge, Massachusetts. weinberg@wi.mit.edu.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Weinberg
mesh_terms: D063646:Carcinogenesis; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism