A division of labor between YAP and TAZ in non-small cell lung cancer

Michal Shreberk-Shaked, Bareket Dassa, Sanju Sinha, Silvia Di Agostino, Ido Azuri, Saptaparna Mukherjee, Yael Aylon, Giovanni Blandino, Eytan Ruppin, Moshe Oren*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Lung cancer is the leading cause of cancer-related deaths worldwide. The paralogous transcriptional cofactors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ, also called WWTR1), the main downstream effectors of the Hippo signal transduction pathway, are emerging as pivotal determinants of malignancy in lung cancer. Traditionally, studies have tended to consider YAP and TAZ as functionally redundant transcriptional cofactors with similar biological impact. However, there is growing evidence that each of them also possesses distinct attributes. Here we sought to systematically characterize the division of labor between YAP and TAZ in non-small cell lung cancer (NSCLC), the most common histological subtype of lung cancer. Representative NSCLC cell lines as well as patient-derived data showed that the two paralogs orchestrated nonoverlapping transcriptional programs in this cancer type. YAP preferentially regulated gene sets associated with cell division and cell-cycle progression, whereas TAZ preferentially regulated genes associated with extracellular matrix organization. Depletion of YAP resulted in growth arrest, whereas its overexpression promoted cell proliferation. Likewise, depletion of TAZ compromised cell migration, whereas its overexpression enhanced migration. The differential effects of YAP and TAZ on key cellular processes were also associated with differential response to anticancer therapies. Uncovering the different activities and downstream effects of YAP and TAZ may thus facilitate better stratification of patients with lung cancer for anticancer therapies.

Original languageEnglish
Pages (from-to)4145-4157
Number of pages13
JournalCancer Research
Issue number19
StatePublished - 1 Oct 2020
Externally publishedYes


FundersFunder number
Anat and Amnon Shashua
DKFZ-MOST Cooperation in Cancer Research
Moross Integrated Cancer Center
Dr. Miriam and Sheldon G. Adelson Medical Research Foundation


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