The role and consequence of having multiple cell types within a cancer is mostly centered towards the function of cancer stem cells (CSCs) since they are the driving forces of tumor growth. However, the exact signaling cues that support CSC function remain to be understood. For instance, what are the roles of differentiated tumor cells in relation to CSC support? We study cell-cell communication between different cell types in human colorectal cancers (CRCs). Our lab develops markers to label CSCs in patient-derived CRC organoids (PDOs) for high-resolution live imaging of their cellular behavior and cell fate dynamics. Currently, we almost exclusively use CRISPR knock-ins for the genetic engineering of PDOs.

Most recently, we used PDOs, genetic mouse models and PDO xenografts, to document the emergence of de novo CSCs during metastasis formation of colon cancer in the liver. Crucially, these cells only appear once a multicellular state is formed, known as micrometastases. Failure to establish CSCs through YAP-controlled epithelial self-organization prohibits the outgrowth of micrometastases.