TMEM9-v-ATPase Activates Wnt/β-Catenin Signaling Via APC Lysosomal Degradation for Liver Regeneration and Tumorigenesis.

ABSTRACT:

Background and aims

How Wnt signaling is orchestrated in liver regeneration and tumorigenesis remains elusive. Recently, we identified transmembrane protein 9 (TMEM9) as a Wnt signaling amplifier.

Approach and results

TMEM9 facilitates v-ATPase assembly for vesicular acidification and lysosomal protein degradation. TMEM9 is highly expressed in regenerating liver and hepatocellular carcinoma (HCC) cells. TMEM9 expression is enriched in the hepatocytes around the central vein and acutely induced by injury. In mice, Tmem9 knockout impairs hepatic regeneration with aberrantly increased adenomatosis polyposis coli (Apc) and reduced Wnt signaling. Mechanistically, TMEM9 down-regulates APC through lysosomal protein degradation through v-ATPase. In HCC, TMEM9 is overexpressed and ne

SUBMITTER: Jung YS 

PROVIDER: S-EPMC7647947 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature