Trophoblastic-like transdifferentiation: A key to oncogenesis

- Cancer cells present strong similarities with physiological invasive trophoblast.
- Trophoblastic master genes are not expressed in normal tissues after birth.
- The hypothesis of their epigenetic reprogramming in cancer cells should be explored.
- A proposal of research aimed at identifying and targeting them is developed.

The epigenetic plasticity of cancer stem-like cells allows them to reprogram multifaceted properties. Being determined by an oncogene driving force, the reprogrammed properties are suitable for extensive, non-homeostatic clone expansion rather than controlled tissue generation. They belong to physiological phenotypes, under strict control in normal cells but illicitly expressed in malignant cells. Comparing the embryo nidation implemented by trophoblast with tumor progression, it clearly appears that trophoblastic and cancerous cells share strongly similar behavior and logistical properties, likely making the trophoblastic phenotype a core component of the malignant phenotype. By reprogramming it, malignant cells acquire a coordinated set of functions very efficient for survival, protection, expansion and migration. This phenotype seems to have not yet been experimentally studied in depth as to its contribution to oncogenesis. We suggest opening a specific field of research on malignant cells and host tissue receptivity, guided by the relationship between nidation and tumor implantation.