TAZ Hijacks Hippo pathway to promote mesenchymal-epithelial transition in pancreatic adenocarcinoma cells.

The Hippo pathway is crucial in organ size control, and its dysregulation contributes to tumorigenesis. TAZ is an essential molecule containing a WW domain in Hippo pathway and serves as transcription co-activator to modulate cell proliferation and induce epithelial-mesenchymal transition in different human cancers, including pancreatic adenocarcinoma. In this study, we found that TAZ, a deletion occurred at its transactivation domain, increases phosphorylation at TAZ Ser89, resulting in sequestration of TAZ in cytoplasm and inhibiting its transcriptional activity.

The regulatory mechanisms and functional roles of the Hippo signaling pathway in breast cancer.

Hippo signaling pathway has attracted broad attention due to its essential roles in controlling organ size and tumorigenesis. TAZ/YAP, two core downstream molecules of the Hippo signaling pathway in mammals, are tightly regulated by a wide range of extracellular and intrinsic signals in both Hippo signaling pathway-dependent and -independent manners. Besides their roles in the development and function of normal mammary glands, TAZ/YAP display remarkable potency and relevance to multiple aspects of human breast carcinogenesis, including cellular proliferation, differentiation, apoptosis, migration, invasion, epithelial-mesenchymal transition and stemness.

Acetylation targets HSD17B4 for degradation via the CMA pathway in response to estrone.

Dysregulation of hormone metabolism is implicated in human breast cancer. 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4) catalyzes the conversion of estradiol (E2) to estrone (E1), and is associated with the pathogenesis and development of various cancers. Here we show that E1 upregulates HSD17B4 acetylation at lysine 669 (K669) and thereby promotes HSD17B4 degradation via chaperone-mediated autophagy (CMA), while a single mutation at K669 reverses the degradation and confers migratory and invasive properties to MCF7 cells upon E1 treatment.

Acetate functions as an epigenetic metabolite to promote lipid synthesis under hypoxia.

Besides the conventional carbon sources, acetyl-CoA has recently been shown to be generated from acetate in various types of cancers, where it promotes lipid synthesis and tumour growth. The underlying mechanism, however, remains largely unknown. We find that acetate induces a hyperacetylated state of histone H3 in hypoxic cells.