2007
DOI: 10.1073/pnas.0611682104
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Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma

Abstract: The cancer stem cell hypothesis suggests that malignant growth depends on a subset of tumor cells with stem cell-like properties of self-renewal. Because hedgehog (Hh) signaling regulates progenitor cell fate in normal development and homeostasis, aberrant pathway activation might be involved in the maintenance of such a population in cancer. Indeed, mutational activation of the Hh pathway is associated with medulloblastoma and basal cell carcinoma; pathway activity is also critical for growth of other tumors … Show more

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Cited by 442 publications
(367 citation statements)
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“…It is also well known that chronic tissue injury caused by inf lammation is associated with tumorigenesis (1). Moreover, recently, it was also shown that Hh signaling maintains a tumor stem cell compartment (34). Therefore, it is possible that, in the early stage of tumorigenesis, Hh signaling promotes cell growth and partially inhibits p53 function, thereby enabling these cells to survive and grow.…”
Section: Discussionmentioning
confidence: 99%
“…It is also well known that chronic tissue injury caused by inf lammation is associated with tumorigenesis (1). Moreover, recently, it was also shown that Hh signaling maintains a tumor stem cell compartment (34). Therefore, it is possible that, in the early stage of tumorigenesis, Hh signaling promotes cell growth and partially inhibits p53 function, thereby enabling these cells to survive and grow.…”
Section: Discussionmentioning
confidence: 99%
“…In addition, ectopic expression of Gli1 or Gli2 in mice results in tumor formation, indicating that activating downstream components of the pathway is sufficient to initiate tumor growth (12). Shh signaling also plays a role in the patho- genesis of chronic myelogenous leukemia, gliomas, and multiple myeloma (13)(14)(15). Shh signaling is active during pancreatic organogenesis, and low level expression of Hip1, Ptch1, Smo, Ihh, and Dhh has been detected within mature islets and cultured cell lines (16,17).…”
mentioning
confidence: 99%
“…In addition, the Gli1 gene is amplified in many sarcomas (16,17) and is expressed at high level in association with the EWS/FLI fusion oncogene that causes Ewing sarcoma (18,19), thus causing activation of Hh pathway targets. Hh pathway activity also appears to be required for the maintenance of cancer stem cells in multiple myeloma (20), chronic myeloid leukemia (21,22), and perhaps other hematologic malignancies (23).…”
mentioning
confidence: 99%