Beclin1-Deficient Adipocytes Promote Tumor Progression by YAP/TAZ-dependent Adipocyte Transformation
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Adipocytes are crucial components of the tumor microenvironment (TME) that play a prominent role in supporting tumor growth. However, the characteristics of cancer-associated adipocytes (CAAs) that contribute to the pro-tumorigenic niche remain to be fully established. Here, we used adipocyte-specific Beclin1 KO (BaKO) mice to investigate the role of maladaptive adipocytes in promoting tumor progression. BECN1-deficient adipocytes exhibited downregulation of adipogenic markers and activation of YAP/TAZ signaling, similar to the traits observed in CAAs. Thus, we generated adipocyte-specific Becn1/Yap1/Taz KO mice, which exhibit markedly restored phenotypes in adipose tissue, resulting in tumor regression compared to that in BaKO. Further, we observed dysregulation of the BECN1-YAP/TAZ axis in the adipose tissue of mice fed a high-fat diet (HFD). Treatment with the YAP/TAZ inhibitor, verteporfin, suppressed tumor progression in BaKO and HFD-fed mice, highlighting its efficacy against mice with metabolic dysregulation. Our findings provide insights into CAA formation and its significance in determining malignant TME, thereby suggesting a potential dual therapeutic strategy simultaneously targeting adipocyte homeostasis and cancer growth.