Essential roles of telomerase reverse transcriptase hTERT in cancer stemness and metastasis

Maintenance of chromosomal telomere length is a hallmark of cancer cells and a prerequisite for stemness. In 85-90% of all human cancers, telomere length maintenance is achieved by reactivation of telomerase, whereas in the remaining 10-15% cancers, alternative lengthening of telomeres (ALT) is observed. Reactivation of telomerase occurs by various mechanisms, one of which is accumulation of point mutations in the promoter region of the gene encoding the protein subunit hTERT. There are numerous studies linking either hTERT overexpression or the presence of hTERT mutations to an aggressive phenotype of several human cancers. Recent findings demonstrate that hTERT expression is not only associated with replicative immortality, but also with cancer cell motility and stem cell phenotype. However, the mechanisms by which hTERT affects cancer cell migration, invasion, and distant metastasis on the one hand, and stemness and resistance on the other hand, are still poorly understood. Within this review, we aim to provide an overview on the functional involvement of hTERT in these cellular processes, focusing on metastasis formation and maintenance of stemness in different human cancers.