| RRC ID |
79484
|
| Author |
Song Y, Na H, Lee SE, Kim YM, Moon J, Nam TW, Ji Y, Jin Y, Park JH, Cho SC, Lee J, Hwang D, Ha SJ, Park HW, Kim JB, Lee HW.
|
| Title |
Dysfunctional adipocytes promote tumor progression through YAP/TAZ-dependent cancer-associated adipocyte transformation.
|
| Journal |
Nat Commun
|
| 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.
|
| Volume |
15(1)
|
| Pages |
4052
|
| Published |
2024-5-14
|
| DOI |
10.1038/s41467-024-48179-3
|
| PII |
10.1038/s41467-024-48179-3
|
| PMID |
38744820
|
| PMC |
PMC11094189
|
| MeSH |
Adaptor Proteins, Signal Transducing* / genetics
Adaptor Proteins, Signal Transducing* / metabolism
Adipocytes* / metabolism
Adipocytes* / pathology
Animals
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism
Cell Transformation, Neoplastic / genetics
Cell Transformation, Neoplastic / metabolism
Cell Transformation, Neoplastic / pathology
Diet, High-Fat* / adverse effects
Disease Progression
Humans
Lipodystrophy / genetics
Lipodystrophy / metabolism
Lipodystrophy / pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout*
Neoplasms / genetics
Neoplasms / metabolism
Neoplasms / pathology
Obesity / metabolism
Obesity / pathology
Signal Transduction
Trans-Activators / genetics
Trans-Activators / metabolism
Transcription Factors / genetics
Transcription Factors / metabolism
Transcriptional Coactivator with PDZ-Binding Motif Proteins
Tumor Microenvironment*
Verteporfin / pharmacology
YAP-Signaling Proteins* / metabolism
|
| Resource |
| Mice |
RBRC02759 |
