(UroToday.com) The International Kidney Cancer Symposium 2021 annual hybrid meeting included a non-clear cell renal cell carcinoma (RCC) session and a presentation by Dr. Kun-Liang Guan discussing the role of NF2 in tumorigenesis and specifically the Hippo pathway and cancer. Dr. Guan started by highlighting that the Hippo pathway plays a key role in organ size control by regulating cell proliferation and apoptosis in Drosophila, the species in which this pathway was first discovered. In work from 2007, Zhao and colleagues1 showed that in mammalian cells, the transcription coactivator YAP (Yes-associated protein), is inhibited by cell density via the Hippo pathway. Phosphorylation by the Lats tumor suppressor kinase leads to cytoplasmic translocation and inactivation of the YAP oncoprotein. Furthermore, attenuation of this phosphorylation of YAP potentiates their growth-promoting function in vivo, with YAP overexpression regulating gene expression in a manner opposite to cell density, and thus overcoming cell contact inhibition. This cellular pathway is highlighted as follows:

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