Illes Bernhard, Fuchs Adrian, Gegenfurtner Florian, Ploetz Evelyn, Zahler Stefan, Vollmar Angelika M, Engelke Hanna
Department of Chemistry and Center for NanoScience (CeNS), Ludwig-Maximilians-Universität München, Butenandtstraße 11, 81377 Munich, Germany.
Department of Pharmacy, Ludwig-Maximilians-Universität München, Butenandtstraße 5, 81377 Munich, Germany.
iScience. 2021 Feb 12;24(3):102185. doi: 10.1016/j.isci.2021.102185. eCollection 2021 Mar 19.
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.
细胞外基质的力学性质强烈影响肿瘤的进展和侵袭。Yes相关蛋白（YAP）已被证明是这一过程的关键调节因子，它将来自细胞外基质的力学信号转化为细胞内信号。尽管YAP在肿瘤进展和转移中具有明显作用，但YAP激活是否能积极触发侵袭的发生尚不清楚。为了解决这个问题，我们设计了一种光可激活的YAP（optoYAP），它可以对其激活进行时空控制。optoYAP的激活机制基于该蛋白的光触发核转位。optoYAP的激活诱导下游信号传导数小时，并导致二维和三维培养物中细胞增殖增加。应用于癌症球体时，optoYAP激活诱导侵袭。在癌症球体中对optoYAP进行位点选择性激活显著地将侵袭引导至激活方向。因此，YAP的核转位可能足以触发侵袭的发生。
