PhD M.P. (Mathijs) Pieter Verhagen

Below is a brief summary of the dissertation:

This thesis investigates phenotypic plasticity in intestinal cancer, with a focus on how epithelial cells modify their characteristics in response to environmental signals, particularly during cancer initiation and metastasis. We explore the impact of inflammation—a significant risk factor for colorectal cancer—on cellular plasticity of differentiated Paneth cells, which can transition into tumor-initiating cells under inflammatory conditions. Our research indicates that secretory goblet cells also play a role in tumorigenesis, with aberrant profiles associated with ulcerative colitis and serrated polyps.
In the second part, we examine the metastatic progression of colorectal cancer, identifying particular cell populations, such as 'Epcam-low' cells, which demonstrate increased plasticity, mobility, and invasiveness. These cells undergo the epithelial-mesenchymal transition, contributing to the disease's aggressive nature. By integrating transcriptomic analyses from clinical specimens with experimental models, this thesis sheds light on the complex mechanisms driving plasticity in cancer and underscores the potential for developing new therapeutic strategies that target phenotypic plasticity in colorectal cancer.