It has become clear that tumours are organised in a cellular hierarchy, with the so-called cancer stem cells (CSC), also called Tumour initiating cells (TICs), being at the apex. It is believed that CSCs mediate tumour growth, precipitate tumour relapse after treatment, and are responsible for metastasis formation. Therefore understanding the molecular mechanisms underlying CSC function may lead to novel therapeutic approaches.
In the last years we made significant contributions to cancer cell biology. We identified a CSC population for luminal breast cancer marked by Lgr6 (Blaas et al., Nature Cell Biology, 2016). Remarkably, Lgr6-posititve CSCs are required to maintain the cellular heterogeneity and malignancy of luminal breast cancer, suggesting that the cellular diversity of luminal breast cancer is generated by CSC, conceptually similar to the function of stem cells in normal organs.
In addition, we shed light on the cell of origin and mechanisms of pancreatic adenocarcinoma (PDAC) development (Gruber et al., Gastroenterology, 2016; Ferreira et al. Cell Reports, 2017), and characterised a CD9-positive CSC population in PDAC which is essential for PDAC ontogenesis (Wang et al., Nature Cell Biology, 2019).
Moreover, we developed a 3D imaging technology termed FLASH that provides unprecedented capabilities to visualise large tissues at single cell resolution. FLASH opened a novel field of experimental 3D tumour imaging, and we used FLASH to obtain fundamental insights into pancreatic tumourigenesis (Messal et al., Nature, 2019).
Future work will focus on using FLASH to characterise tumour development and relapse, understanding the molecular mechanism underlying CSC function, and to identify CSC vulnerabilities which can be therapeutically exploited.