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Multiple Tumor Suppressor Pathways Negatively Regulate Telomerase

Lin, Shiaw-Yih, Elledge, Stephen J·2003·Cell
DOI 10.1016/s0092-8674(03)00430-6
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Abstract

Telomerase expression is repressed in most somatic cells but is observed in stem cells and a high percentage of human cancers and has been hypothesized to contribute to tumorigenesis and maintenance of stem cell states. To explore telomerase regulation, we employed a general genetic screen to identify negative regulators of hTERT. We discovered three tumor suppressor/oncogene pathways involved in hTERT repression. One, the Mad1/c-Myc pathway, had been previously implicated in hTERT regulation. The second, SIP1, a transcriptional target of the TGF-beta pathway, mediates the TGF-beta regulated repression of hTERT. The third, the tumor suppressor Menin, is a direct repressor of hTERT. Depleting Menin immortalizes primary human fibroblasts and causes a transformation phenotype when coupled with expression of SV40 Large and Small T antigen and oncogenic ras. These studies suggest that multiple tumor suppressor/oncogene pathways coordinately repress hTERT expression and imply that telomerase is reactivated in human tumors through oncogenic mutations.

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Metadata

Authors
Lin, S.-Y., & Elledge, S. J.
Venue
Cell
Publisher
Elsevier BV
Published
2003-06
Volume
113
Issue
7
Pages
881-889
ISSN
0092-8674
DOI
10.1016/s0092-8674(03)00430-6
Cited by
363
References
16
Language
en
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CoChat. (2026). Citation check: Multiple Tumor Suppressor Pathways Negatively Regulate Telomerase. https://app.cochat.ai/papers/10.1016/s0092-8674(03)00430-6
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Lin, S.-Y., & Elledge, S. J. (2003). Multiple Tumor Suppressor Pathways Negatively Regulate Telomerase. Cell. https://doi.org/10.1016/s0092-8674(03)00430-6