Noncanonical role of Golgi-associated macrophage TAZ in chronic inflammation and tumorigenesis
Until now, Hippo pathway-mediated nucleocytoplasmic translocation has been considered the primary mechanism by which yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) transcriptional coactivators regulate cell proliferation and differentiation via transcriptional enhanced associate domain (TEAD)-mediated target gene expression. In this study, however, we found that TAZ, but not YAP, is associated with the Golgi apparatus in macrophages activated via Toll-like receptor ligands during the resolution phase of inflammation. Golgi-associated TAZ enhanced vesicle trafficking and secretion of proinflammatory cytokines in M1 macrophage independent of the Hippo pathway. Depletion of TAZ in tumor-associated macrophages promoted tumor growth by suppressing the recruitment of tumor-infiltrating lymphocytes. Moreover, in a diet-induced metabolic dysfunction-associated steatohepatitis model, macrophage-specific deletion of TAZ ameliorated liver inflammation and hepatic fibrosis. Thus, targeted therapies being developed against YAP/TAZ-TEAD are ineffective in macrophages. Together, our results introduce Golgi-associated TAZ as a potential molecular target for therapeutic intervention to treat tumor progression and chronic inflammatory diseases.
Authors
- Sang‐Jun Ha (ORCID: https://orcid.org/0000-0002-1192-6031)
- Hyeran Shim (ORCID: https://orcid.org/0009-0005-5951-991X)
- Hyeok-Gu Kang (ORCID: https://orcid.org/0000-0002-3187-6844)
- Kun‐Liang Guan (ORCID: https://orcid.org/0000-0003-1892-0174)
- Sungeun Ju (ORCID: https://orcid.org/0000-0002-8597-3850)
- Hwa-Ryeon Kim (ORCID: https://orcid.org/0000-0001-9418-7061)
- Kyung‐Hee Chun (ORCID: https://orcid.org/0000-0002-9867-7321)
- Jae‐Seok Roe (ORCID: https://orcid.org/0000-0002-9994-3062)
- D. Park (ORCID: https://orcid.org/0009-0009-4272-1846)
- Junjeong Choi (ORCID: https://orcid.org/0000-0003-1339-593X)
- Heon Yung Gee (ORCID: https://orcid.org/0000-0002-8741-6177)
- Hyun Woo Park (ORCID: https://orcid.org/0000-0001-7736-2286)
- Ji Eun Paik (ORCID: https://orcid.org/0009-0003-8219-5090)
- S. Park (ORCID: https://orcid.org/0009-0007-5007-9094)
- Han‐Woong Lee (ORCID: https://orcid.org/0000-0001-9515-3605)
- Ji Eun Shin (ORCID: https://orcid.org/0000-0002-0409-0774)
- Jae Hoon Lee (ORCID: https://orcid.org/0000-0001-9777-5918)
- Young-Joon Kim (ORCID: https://orcid.org/0000-0001-5061-587X)
- Dong Hyeon Kim (ORCID: https://orcid.org/0009-0000-8446-4352)
- Seok Chan Cho (ORCID: https://orcid.org/0009-0004-7764-2017)
- Seung‐Yeol Park (ORCID: https://orcid.org/0000-0001-5061-4535)
- Doru Kwon (ORCID: https://orcid.org/0009-0007-6595-4533)
- Yujin Sub
- Seyeon Park (ORCID: https://orcid.org/0009-0002-3393-9922)
Institutions
- Pohang University of Science and Technology (KR)
- Yonsei University (KR)
- Korea University Medical Center (KR)
- Westlake University (CN)
Publication Details
- Journal
- Science Advances
- Published
- 2025-01-22
- DOI
- https://doi.org/10.1126/sciadv.adq2395
- Citations
- 4
- Primary Topic
- Hippo pathway signaling and YAP/TAZ
- Type
- article
- Field-Weighted Citation Impact
- 4.61