Cell reprogramming in cancer: Interplay of genetic, epigenetic mechanisms, and the tumor microenvironment in carcinogenesis and metastasis

Figure 1 This schematic highlights the dynamic plasticity of cancer cells and their ability to reprogram, contributing to tumor progression and therapy resistance. Cancer initiation begins with a cell of origin, which is the first cell in a tissue to acquire a cancer-initiating driver mutation. This cell can be a normal native stem cell, a common/committed progenitor, or a fully differentiated cell. Driver mutations (indicated by red starbursts) can occur at any stage of cell differentiation, leading to malignant transformation. The result is a heterogenous tumor consisting of cell of origin, cancer stem cells, blood vessels, immune cells. De-differentiation refers to the reprogramming of a specialized cell into a less specialized state, reverting to a progenitor or stem-like phenotype within the same lineage. Trans-differentiation occurs when a differentiated cell reprograms into another differentiated cell type, potentially from a different lineage, as observed in treatment-induced neuroendocrine prostate cancer.