YAP regulates an SGK1/mTORC1/SREBP-dependent lipogenic program to support proliferation and tissue growth

Vaidyanathan, S; Salmi, TM; Sathiqu, RM; McConville, MJ; Cox, AG; Brown, KK

Author(s): Vaidyanathan, S; Salmi, TM; Sathiqu, RM; McConville, MJ; Cox, AG; Brown, KK;
Details: Publication Year 2022-03-28,Volume 57,Issue #6,Page 719-731.e8
Journal Title: Developmental Cell
Publication Type: Research article
Abstract: The coordinated regulation of growth control and metabolic pathways is required to meet the energetic and biosynthetic demands associated with proliferation. Emerging evidence suggests that the Hippo pathway effector Yes-associated protein 1 (YAP) reprograms cellular metabolism to meet the anabolic demands of growth, although the mechanisms involved are poorly understood. Here, we demonstrate that YAP co-opts the sterol regulatory element-binding protein (SREBP)-dependent lipogenic program to facilitate proliferation and tissue growth. Mechanistically, YAP stimulates de novo lipogenesis via mechanistic target of rapamcyin (mTOR) complex 1 (mTORC1) signaling and subsequent activation of SREBP. Importantly, YAP-dependent regulation of serum- and glucocorticoid-regulated kinase 1 (SGK1) is required to activate mTORC1/SREBP and stimulate de novo lipogenesis. We also find that the SREBP target genes fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD) are conditionally required to support YAP-dependent proliferation and tissue growth. These studies reveal that de novo lipogenesis is a metabolic vulnerability that can be targeted to disrupt YAP-dependent proliferation and tissue growth.
Keywords: Cell Proliferation; *Lipogenesis/genetics; Mechanistic Target of Rapamycin Complex 1/metabolism; Sterol Regulatory Element Binding Protein 1/genetics/metabolism; *Sterol Regulatory Element Binding Proteins/genetics/metabolism; Sgk1; Srebp; Yap; cell metabolism; growth; lipogenesis; mTORC1; proliferation
Department(s): Laboratory Research
PubMed ID: 35216681
Publisher's Version: https://doi.org/10.1016/j.devcel.2022.02.004
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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