Josh L. Stern Assistant professor, University of Alabama, Birmingham

Josh L. Stern Assistant professor, University of Alabama, Birmingham

Josh L. Stern Assistant professor, University of Alabama, Birmingham Josh L. Stern Assistant professor, University of Alabama, Birmingham
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Stem cell theory

Is there a stem cell origin for some cancer cells?

Some cancers may arise from stem cells that sustain oncogenic mutations. In such a scenario, telomerase would be expressed by these cells before these oncogenic mutations; it would also continue to be expressed afterwards. Thus, if this hypothesis is correct, then these cells would have never undergone transcriptional silencing of telomerase. It is important to ascertain if this hypothesis is correct as it may elucidate the fundamental nature of these cancers. For example, some data indicate that such cancer stem cells are especially resistant to certain anti-cancer therapies. If this hypothesis is true, then this may be important for understanding how to stratify patients based on the origin of their cancers. In addition, by testing this hypothesis, we may learn much about the regulation of telomerase in cancer. 


Alternatively, some cancers may derive from differentiated cells that sustain mutations that then drive the acquisition of stem cell-like characteristics. In such cells, since the TERT gene was transcriptionally silent in the differentiated state, telomerase may require reactivation. It is hypothesized that this reactivation may be driven by the (i) acquisition of activation mutations, (ii) alteration of the transcriptional machinery at TERT and/or (iii) epigenetic depression of the TERT gene due to loss of epigenetic homeostasis.


In any of these scenarios, telomerase is very likely to be the mechanism supporting the long term self-renewal of these cancer stem cells, and as such may be vulnerable to telomerase inhibitors.