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Nat. Commun., May 14 2024, 15 (1) | https://doi.org/10.1038/s41467-024-48179-3
Dysfunctional adipocytes promote tumor progression through YAP/TAZ-dependent cancer-associated adipocyte transformation
Yaechan Song1,4, Heeju Na1,4, Seung Eon Lee1, You Min Kim1, Jihyun Moon1, Tae Wook Nam1, Yul Ji2, Young Jin1, Jae Hyung Park1, Seok Chan Cho1, Jaehoon Lee1,3, Daehee Hwang2, Sang-Jun Ha1, Hyun Woo Park1, Jae Bum Kim2 & Han-Woong Lee1,3
1Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.
2Department of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea.
3Gemcro, Inc, Seoul 03722, Republic of Korea.
4These authors contributed equally: Yaechan Song, Heeju Na.
Corresponding author
Correspondence to Han-Woong Lee.
Abstract
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.
논문정보
- Research article
- 2024년 05월 (BRIC 등록일 2024-05-16)
- 국내 연구진
- 생명과학 > 세포생물학
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