The progression of cancer and metastasis formation: An epigenetic hypothesis

• A new hypotheses for the origin of metastasis is proposed.
• Cancer stem cells could be involved in metastasis formation.
• Epigenetic marks and chromatin reorganization could have a main role in metastasis.

The molecular mechanisms of tumor metastasis remain largely unknown and undefined. A recent model suggests that a minor population of cells (cancer stem cells) is programmed to preferentially metastasize to specific organs based on their gene expression patterns. These cells have the ability to generate tumors after implantation into animal hosts, to self-renew and give rise to non-stem cells. In this paper I hypothesize that epigenetic mechanisms could play an important role in tumor metastasis through the reorganization of the bivalent chromatin marks in cancer stem cells in three phases: 1) the reprogramming of epigenetic marks in differentiation master regulator genes responsible for the differentiation to one particular lineage 2) the resolution of these bivalent chromatin marks forces cells to develop the necessary mechanisms to migrate to a new niche and 3) the epigenetic activation of the tissue-specific genes associated with the specific target organ and, simultaneously, the repression of genes associated with alternative developmental pathways.

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