2. Academic Validation
  3. Noncanonical role of Golgi-associated macrophage TAZ in chronic inflammation and tumorigenesis

Noncanonical role of Golgi-associated macrophage TAZ in chronic inflammation and tumorigenesis

  • Sci Adv. 2025 Jan 24;11(4):eadq2395. doi: 10.1126/sciadv.adq2395.
So Yeon Park 1,  Sungeun Ju 2,  Jaehoon Lee 1 3,  Hwa-Ryeon Kim 1,  Yujin Sub 4,  Dong Jin Park 1,  Seyeon Park 1,  Doru Kwon 5,  Hyeok Gu Kang 6,  Ji Eun Shin 1,  Dong Hyeon Kim 1,  Ji Eun Paik 1,  Seok Chan Cho 1,  Hyeran Shim 1,  Young-Joon Kim 1,  Kun-Liang Guan 7,  Kyung-Hee Chun 6,  Junjeong Choi 5,  Sang-Jun Ha 1,  Heon Yung Gee 4,  Jae-Seok Roe 1,  Han-Woong Lee 1 3,  Seung-Yeol Park 2,  Hyun Woo Park 1
Affiliations

Affiliations

  • 1 Department of Biochemistry, College of Life Science and Biotechnology, Brain Korea 21 Project, Yonsei University, Seoul 03722, Republic of Korea.
  • 2 Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea.
  • 3 Gemcro Inc., Seoul 03722, Republic of Korea.
  • 4 Department of Pharmacology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
  • 5 College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of Korea.
  • 6 Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Republic of Korea.
  • 7 School of Life Sciences, Westlake University, Hangzhou 310030, China.
PMID: 39841821 DOI: 10.1126/sciadv.adq2395
Abstract

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.

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