Several studies have shown that cancer cells can be "phenotypically reversed", thus achieving a "tumor reversion", by losing malignant hallmarks as migrating and invasive capabilities. These findings suggest that genome activity can switch to assume a different functional configuration, i.e. a different Gene Regulatory Network pattern. Indeed, once "destabilized", cancer cells enter into a critical transition phase that can be adequately "oriented" by yet unidentified morphogenetic factors - acting on both cells and their microenvironment - that trigger an orchestrated array of structural and epigenetic changes. Such process can bypass genetic abnormalities, through rerouting cells toward a benign phenotype. Oocytes and embryonic tissues, obtained by animals and humans, display such "reprogramming" capability, as a number of yet scarcely identified embryo-derived factors can revert the malignant phenotype of several types of tumors. Mechanisms involved in the reversion process include the modification of cell-microenvironment cross talk (mostly through cytoskeleton reshaping), chromatin opening, demethylation, and epigenetic changes, modulation of biochemical pathways, comprising TCTP-p53, PI3K-AKT, FGF, Wnt, and TGF-8-dependent cascades. Results herein discussed promise to open new perspectives not only in the comprehension of cancer biology but also toward different therapeutic options, as suggested by a few preliminary clinical studies.
Tumor reversion and embryo morphogenetic factors / Proietti, Sara; Cucina, Alessandra; Pensotti, Andrea; Fuso, Andrea; Marchese, Cinzia; Nicolini, Andrea; Bizzarri, Mariano. - In: SEMINARS IN CANCER BIOLOGY. - ISSN 1044-579X. - 79:(2022), pp. 83-90. [10.1016/j.semcancer.2020.09.005]
Tumor reversion and embryo morphogenetic factors
Cucina, Alessandra;Fuso, Andrea;Marchese, Cinzia;Nicolini, Andrea;Bizzarri, Mariano
2022
Abstract
Several studies have shown that cancer cells can be "phenotypically reversed", thus achieving a "tumor reversion", by losing malignant hallmarks as migrating and invasive capabilities. These findings suggest that genome activity can switch to assume a different functional configuration, i.e. a different Gene Regulatory Network pattern. Indeed, once "destabilized", cancer cells enter into a critical transition phase that can be adequately "oriented" by yet unidentified morphogenetic factors - acting on both cells and their microenvironment - that trigger an orchestrated array of structural and epigenetic changes. Such process can bypass genetic abnormalities, through rerouting cells toward a benign phenotype. Oocytes and embryonic tissues, obtained by animals and humans, display such "reprogramming" capability, as a number of yet scarcely identified embryo-derived factors can revert the malignant phenotype of several types of tumors. Mechanisms involved in the reversion process include the modification of cell-microenvironment cross talk (mostly through cytoskeleton reshaping), chromatin opening, demethylation, and epigenetic changes, modulation of biochemical pathways, comprising TCTP-p53, PI3K-AKT, FGF, Wnt, and TGF-8-dependent cascades. Results herein discussed promise to open new perspectives not only in the comprehension of cancer biology but also toward different therapeutic options, as suggested by a few preliminary clinical studies.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.