Epithelial–mesenchymal transition machinery and stemness markers in colorectal cancer cells

The epithelial–mesenchymal transition (EMT) machinery and stemness markers in colorectal cancer (CRC) represent a complex network of molecular drivers that facilitate tumor progression, metastasis, and therapeutic resistance. EMT is a biological process where polarized epithelial cells lose their adhesion properties and undergo biochemical changes to assume a mesenchymal phenotype, which is characterized by increased migratory capacity and invasiveness (Vargas et al., 2020, Cancers). This transition is frequently associated with the acquisition of stem-like properties, where specific markers such as CD44, CD133, and LGR5 identify a subpopulation of cancer stem cells (CSCs) capable of self-renewal and tumor initiation (Tirino et al., 2013, FEBS Letters). Key molecular components of this machinery include transcription factors like Snail, Slug, and Twist, as well as signaling cascades such as TGF-beta, Wnt, and Notch (Pastushenko & Blanpain, 2019, Trends in Cell Biology). In the context of drug development, these markers and pathways are targeted to eliminate the highly resistant CSC population and prevent the metastatic spread of CRC. For example, STAT3 inhibitors like Napabucasin have been investigated for their ability to inhibit stemness gene expression, while TGF-beta inhibitors like Galunisertib aim to block the primary driver of EMT (Li et al., 2015, PNAS). However, targeting these mechanisms presents significant challenges, as many of the involved pathways are essential for normal tissue homeostasis and wound healing. Furthermore, the inherent plasticity of cancer cells allows them to transition between epithelial, mesenchymal, and stem-like states, complicating the efficacy of single-target therapies.

Other names

EMT-CSC axis in colorectal cancerColorectal cancer stemness markersEMT-related proteins in CRC

Inhibition of signaling pathways such as TGF-beta, Wnt/beta-catenin, Notch, and STAT3 to suppress the transition of epithelial cells to a mesenchymal state and deplete the cancer stem cell population.