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
  • 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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