Cancer stem cells are the cancer cells that have abilities to self-renew, differentiate into defined progenies, and initiate and maintain tumor growth. They also contribute to cancer metastasis and therapeutic resistance, both of which are the major causes of cancer mortality. Among the reported makers of the cancer stem cells, CD133 is the most well-known marker for isolating and studying cancer stem cells in different types of cancer. The CD133high population of cancer cells are not only capable of self-renewal, proliferation, but also highly metastatic and resistant to therapy. Despite very limited information on physiological functions of CD133, many ongoing studies are aimed to reveal the mechanisms that CD133 utilizes to modulate cancer dissemination and drug resistance with a long-term goal for bringing down the number of cancer deaths. In this review, in addition to the regulation of CD133, and its involvement in cancer initiation, and development, the recent updates on how CD133 modulates cancer dissemination, and therapeutic resistance are provided. The key signaling pathways that are upstream or downstream of CD133 during these processes are summarized. A comprehensive understanding of CD133-mediated cancer initiation, development, and dissemination through its pivotal role in cancer stem cells will offer new strategies in cancer therapy.
Keywords: CD133; CD44; Cancer initiation; Cancer stem cell; DCLK1; Metastasis; PROM1; Signal transduction; Therapeutic resistance; Tumor development.
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