Spatio-selective activation of nuclear translocation of YAP with light directs invasion of cancer cell spheroids

Illes, Bernhard; Fuchs, Adrian; Gegenfurtner, Florian; Plötz, Evelyn; Zahler, Stefan; Vollmar, Angelika M. und Engelke, Hanna (2021): Spatio-selective activation of nuclear translocation of YAP with light directs invasion of cancer cell spheroids. In: Iscience, Bd. 24, Nr. 3, 102185

Abstract

The mechanical properties of the extracellular matrix strongly influence tumor progression and invasion. Yes-associated protein (YAP) has been shown to be a key regulator of this process translating mechanical cues from the extracellular matrix into intracellular signals. Despite its apparent role in tumor progression and metastasis, it is not clear yet, whether YAP activation can actively trigger the onset of invasion. To address this question, we designed a photo-activatable YAP (optoYAP), which allows for spatiotemporal control of its activation. The activation mechanism of optoYAP is based on optically triggered nuclear translocation of the protein. Activation of optoYAP induces downstream signaling for several hours and leads to increased proliferation in two- and three-dimensional cultures. Applied to cancer spheroids, optoYAP activation induces invasion. Site-selective activation of optoYAP in cancer spheroids strikingly directs invasion into the activated direction. Thus, nuclear translocation of YAP may be enough to trigger the onset of invasion.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department Chemie
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• Sprache: Englisch