Dysfunctional adipocytes promote tumor progression through YAP/TAZ-dependent cancer-associated adipocyte transformation.

Autor: Song Y; Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea., Na H; Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea., Lee SE; Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea., Kim YM; Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea., Moon J; Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea., Nam TW; Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea., Ji Y; Department of Biological Sciences, Seoul National University, Seoul, 08826, Republic of Korea., Jin Y; Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea., Park JH; Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea., Cho SC; Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea., Lee J; Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea.; Gemcro, Inc, Seoul, 03722, Republic of Korea., Hwang D; Department of Biological Sciences, Seoul National University, Seoul, 08826, Republic of Korea., Ha SJ; Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea., Park HW; Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea., Kim JB; Department of Biological Sciences, Seoul National University, Seoul, 08826, Republic of Korea., Lee HW; Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea. hwl@yonsei.ac.kr.; Gemcro, Inc, Seoul, 03722, Republic of Korea. hwl@yonsei.ac.kr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 May 14; Vol. 15 (1), pp. 4052. Date of Electronic Publication: 2024 May 14.
DOI: 10.1038/s41467-024-48179-3
Abstrakt: Obesity has emerged as a prominent risk factor for the development of malignant tumors. However, the existing literature on the role of adipocytes in the tumor microenvironment (TME) to elucidate the correlation between obesity and cancer remains insufficient. Here, we aim to investigate the formation of cancer-associated adipocytes (CAAs) and their contribution to tumor growth using mouse models harboring dysfunctional adipocytes. Specifically, we employ adipocyte-specific BECN1 KO (BaKO) mice, which exhibit lipodystrophy due to dysfunctional adipocytes. Our results reveal the activation of YAP/TAZ signaling in both CAAs and BECN1-deficient adipocytes, inducing adipocyte dedifferentiation and formation of a malignant TME. The additional deletion of YAP/TAZ from BaKO mice significantly restores the lipodystrophy and inflammatory phenotypes, leading to tumor regression. Furthermore, mice fed a high-fat diet (HFD) exhibit decreased BECN1 and increased YAP/TAZ expression in their adipose tissues. Treatment with the YAP/TAZ inhibitor, verteporfin, suppresses tumor progression in BaKO and HFD-fed mice, highlighting its efficacy against mice with metabolic dysregulation. Overall, our findings provide insights into the key mediators of CAA and their significance in developing a TME, thereby suggesting a viable approach targeting adipocyte homeostasis to suppress cancer growth.
(© 2024. The Author(s).)
Databáze: MEDLINE
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