Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 23, Pages -Publisher
MDPI
DOI: 10.3390/ijms232314610
Keywords
cancer genesis and progression; LINE-1 retrotransposons; reverse transcriptase (RT); RT inhibitors; autophagy; nuclear lamina; chromatin; genome expression; embryogenesis
Funding
- Fondazione Roma
- CNR National Research Council [DSB.AD007.219.002]
- MUR-PRIN [2017FNZRN3_005-LS2]
Ask authors/readers for more resources
In the past fifty years, significant progress has been made in understanding the molecular mechanisms of cancer and developing effective therapies. Research suggests that the onset and progression of cancer are influenced by a stress-responsive epigenetic mechanism, resulting in genome plasticity and global gene expression reprogramming. These findings improve our understanding of cancer and may lead to new treatment approaches.
In the last fifty years, large efforts have been deployed in basic research, clinical oncology, and clinical trials, yielding an enormous amount of information regarding the molecular mechanisms of cancer and the design of effective therapies. The knowledge that has accumulated underpins the complexity, multifactoriality, and heterogeneity of cancer, disclosing novel landscapes in cancer biology with a key role of genome plasticity. Here, we propose that cancer onset and progression are determined by a stress-responsive epigenetic mechanism, resulting from the convergence of upregulation of LINE-1 (long interspersed nuclear element 1), the largest family of human retrotransposons, genome damage, nuclear lamina fragmentation, chromatin remodeling, genome reprogramming, and autophagy activation. The upregulated expression of LINE-1 retrotransposons and their protein products plays a key role in these processes, yielding an increased plasticity of the nuclear architecture with the ensuing reprogramming of global gene expression, including the reactivation of embryonic transcription profiles. Cancer phenotypes would thus emerge as a consequence of the unscheduled reactivation of embryonic gene expression patterns in an inappropriate context, triggering de-differentiation and aberrant proliferation in differentiated cells. Depending on the intensity of the stressing stimuli and the level of LINE-1 response, diverse degrees of malignity would be generated.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available