Abstract
The recent identification of tumor-initiating colorectal cancer (CRC) stem cells in the pathogenesis of CRC has provided a potential target for novel therapeutics. Many details about CRC stem cells, however, remain poorly understood. Several potential markers of CRC stem cells have been proposed, including CD133, CD44, and, recently, Lgr5. Attention also has been drawn to control of stem cell self-renewal, proliferation, and differentiation by the Wnt and transforming growth factor (TGF)-β pathways. Disruption of Wnt signaling, via loss of APC (adenomatous polyposis coli), is among the earliest events in the multistage progression of CRC and likely occurs in basal crypt stem cells, generating a neoplastic cell population that then expands upward to occupy the rest of the crypt. TGF-β signaling is a key tumor suppressor pathway, and mutations in the type II receptor and Smad4 are observed in CRC specimens and are associated with more aggressive disease in tumors with disrupted Wnt signaling. Loss of the TGF-β adaptor protein β(2)-spectrin is associated with loss of colonic cell polarity and architecture, and its expression parallels that of Smad4. This review suggests rational approaches to target CRC stem cells as a novel and effective way to treat advanced and difficult-to-treat CRC.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
