TGF-β/SMAD canonical pathway induces the expression of transcriptional cofactor TAZ in liver cancer cells

Heliyon. 2023 Oct 31;9(11):e21519. doi: 10.1016/j.heliyon.2023.e21519. eCollection 2023 Nov.

Abstract

The TGF-β and Hippo pathways are critical for liver size control, regeneration, and cancer progression. The transcriptional cofactor TAZ, also named WWTR1, is a downstream effector of Hippo pathway and plays a key role in the maintenance of liver physiological functions. However, the up-regulation of TAZ expression has been associated with liver cancer progression. Recent evidence shows crosstalk of TGF-β and Hippo pathways, since TGF-β modulates TAZ expression through different mechanisms in a cellular context-dependent manner but supposedly independent of SMADs. Here, we evaluate the molecular interplay between TGF-β pathway and TAZ expression and observe that TGF-β induces TAZ expression through SMAD canonical pathway in liver cancer HepG2 cells. Therefore, TAZ cofactor is a primary target of TGF-β/SMAD-signaling, one of the pathways altered in liver cancer.

Keywords: HepG2 cells; Hippo-pathway; Liver cancer; TAZ cofactor; TGF-β cytokine.