Article
Version 1
Preserved in Portico This version is not peer-reviewed
Identification of a Gene Signature That Predicts Dependence upon YAP/TAZ-TEAD
Version 1
: Received: 27 December 2023 / Approved: 28 December 2023 / Online: 29 December 2023 (14:38:27 CET)
A peer-reviewed article of this Preprint also exists.
Kanai, R.; Norton, E.; Stern, P.; Hynes, R.O.; Lamar, J.M. Identification of a Gene Signature That Predicts Dependence upon YAP/TAZ-TEAD. Cancers 2024, 16, 852. Kanai, R.; Norton, E.; Stern, P.; Hynes, R.O.; Lamar, J.M. Identification of a Gene Signature That Predicts Dependence upon YAP/TAZ-TEAD. Cancers 2024, 16, 852.
Abstract
Targeted therapies are effective cancer treatments when accompanied by accurate diagnostic tests that can help identify patients that will respond to those therapies. The YAP/TAZ-TEAD axis is activated and plays a causal role in several cancer types, and TEAD inhibitors are currently in early phase clinical trials in cancer patients. However, mutations that predict YAP/TAZ-TEAD activation are not commonly found in most cancer types, making it hard to determine which tumors are de-pendent upon YAP/TAZ-TEAD. Here, we used a combination of RNA-seq and bioinformatics analysis of metastatic melanoma cells to develop a YAP/TAZ gene signature. We found that the genes in this signature are TEAD-dependent, and that their expression strongly correlates with YAP/TAZ activation in human melanomas. Using DepMap dependency data, we found that this YAP/TAZ signature was predictive of melanoma cell dependence upon YAP/TAZ or TEADs. Importantly, this was not limited to melanoma because this signature was also predictive when tested on a panel of over 1000 cancer cell lines representing numerous distinct cancer types. Our results suggest that YAP/TAZ gene signatures like ours may be an effective tool to predict tumor cell sensitivity to YAP/TAZ-TEAD inhibition, and thus provide a means to identify patients likely to benefit from TEAD inhibitors.
Keywords
YAP; TAZ; WWTR1; TEAD; metastasis; melanoma; Hippo; Gene Signature
Subject
Biology and Life Sciences, Cell and Developmental Biology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Comments (0)
We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.
Leave a public commentSend a private comment to the author(s)
* All users must log in before leaving a comment