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Sci. Adv., 22 Jan 2025 | https://doi.org/10.1126/sciadv.adq2395 Noncanonical role of Golgi-associated macrophage TAZ in chronic inflammation and tumorigenesis

So Yeon Park ¹, Sungeun Ju², 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 *}

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

^*Corresponding author: correspondence to Hyun Woo Park

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.

논문정보

형식Research article
게재일2025년 01월 (BRIC 등록일 2025-01-23)
연구진국내(교신)+국외 연구진
분야 생명과학 > 분자생물학

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