Integrins play an essential role in multicellular life by connecting cells to the extracellular matrix. This thesis provides an overview of the distinct types of integrin-containing cell adhesion... Show moreIntegrins play an essential role in multicellular life by connecting cells to the extracellular matrix. This thesis provides an overview of the distinct types of integrin-containing cell adhesion complexes present in epithelial cells. By employing BioID we succesfully characterized the composition of focal adhesions, flat clathrin lattices, and hemidesmosomes. In addition, we investigated the role of different adhesion complexes in (cancer) cell adhesion, migration, polarity, and proliferation and in mechanotransduction. Show less
In this thesis, we aim to shed light on the diverse and often opposing roles of integrin α3β1 in cancer. Our work highlights that the role of α3β1 in cancer depends on time and place: the nature of... Show moreIn this thesis, we aim to shed light on the diverse and often opposing roles of integrin α3β1 in cancer. Our work highlights that the role of α3β1 in cancer depends on time and place: the nature of the cell environment (such as extracellular matrix composition), type of cancer and its driving mechanism, as well as the stage of the disease. We provide a new insight into the mechanisms behind the role of α3β1 in HER2-driven breast cancer and in DMBA/TPA-induced non-melanoma skin tumorigenesis. Show less
The first use of birch tar adhesives by Neandertals over 191,000 years ago marked a significant technological development. The ability to produce entirely new materials through transformative... Show moreThe first use of birch tar adhesives by Neandertals over 191,000 years ago marked a significant technological development. The ability to produce entirely new materials through transformative processes was unlike anything that had been done before. In southern Africa, during the Middle Stone Age, humans made compound adhesives by combining disparate ingredients, a task which is believed to have required modern-like levels of cognition. However, for all of the significance given to ancient adhesives in discussions about Neandertal and modern human technological and cognitive capabilities, our knowledge of the material itself is limited. This thesis provides the first comprehensive study of Middle Palaeolithic and Middle Stone Age adhesives, providing new insight into the material choices and technological capabilities of Neandertals and Middle Stone Age humans. Finally, as awareness for the importance of Palaeolithic adhesive residues continues to increase, and more discoveries are made, new questions and materials that need to be tested are constantly being brought to light. Show less
Tissues are dynamic groups of cells with specific functions for each cell type. A disturbed communication between the cells of the same or different type can lead to a variety of diseases, for... Show moreTissues are dynamic groups of cells with specific functions for each cell type. A disturbed communication between the cells of the same or different type can lead to a variety of diseases, for example cancer. This thesis describes the fading border between adhesion molecules and adhesion receptors. The characteristics of a relatively novel epithelial morphoregulating molecule, Ep-CAM, are presented, as well as its role in tumor biology are reviewed. E-cadherin mediated adhesion complex is abrogated by introduction of Ep-CAM, without involvement of key regulator beta-catenin. The signaling transduction pathway includes activation of Pi3K. Iimmunohistochemistry studies of EpCAM expression in tumors showed that Ep-CAM is a useful diagnostic marker for the identification of neoplastic epithelial changes and tumors of epithelial origin. Furthermore, the effect of Ep-CAM on cadherin mediated adhesions is reversible. The restauration of cadherin mediated adhesions by suppressing the Ep-CAM expression, is of great importance in the quest for new modalities for curing cancer. Show less
Cortactine wordt gecodeerd door het gen EMS1 dat op het chromosoom 11q13 ligt. Het 11q13 gebied is geamplificeerd in een deel van de borsttumoren dat geassocieerd is met cortactine overexpressie en... Show moreCortactine wordt gecodeerd door het gen EMS1 dat op het chromosoom 11q13 ligt. Het 11q13 gebied is geamplificeerd in een deel van de borsttumoren dat geassocieerd is met cortactine overexpressie en de aanwezigheid van lymfeklier metastasen en een verhoogde sterfte. Cortactine is een F-actine bindend eiwit dat betrokken is bij de regulatie van het actine cytoskelet, dat belangrijk is bij cel migratie. Agnes van Rossum onderzocht de rol van cortactine (over)expressie op cel biologische processen die betrokken zijn bij de ontwikkeling en/of het gedrag van borstkanker. Zij ontdekte onder meer dat er cortactine varianten zijn die de cel migratie beïnvloeden. Verder lijkt cortactine een rol te spelen bij intercellulaire cel adhesie en cel spreiding. Een studie met cortactine transgene muizen toonde aan dat cortactine geen oorzakelijke rol heeft in het ontstaan van borstkanker. Van Rossum vermoedt dat cortactine de binding tussen cellen en hun omgeving dusdanig kan beïnvloeden dat deze gemakkelijker uit de oorspronkelijke tumor kunnen ontsnappen en gaan migreren. Show less
