Mechanisms of cancer transdifferentiation

Abstract

During cancer progression, cells undergo cell state changes, which contribute towards malignancy, tumor growth and metastasis. Cell state transitions in cancer occurs when cells either undergo epithelial-to-mesenchymal transition (EMT) to become more cellularly plastic in the mesenchymal state or undergo mesenchymal-to-epithelial transition (MET) to revert back into the highly proliferative epithelial state. The ability of cancer cells to readily undergo cell state changes attributes significantly to tumor aggression. The perturbation of cell state transitions, therefore, represents an attractive strategy for cancer therapeutics. Current approaches in cancer therapeutics focuses on blocking EMT, thereby preventing metastasis and relapse, or inducing MET, which converts the treatment-resistant mesenchymal cells back into a treatment-sensitive epithelial state. However, transdifferentiation in cancer is a new frontier in cellular differentiation, which could potentially ablate the metastatic capabilities and stump tumor growth in these cancer cells. Thus, highlighting the clinical potential of transdifferentiation in cancer.