Autophagic protein ULK1 regulates FOXM1 signalling in human hepatoma cells.

Journal Article (Journal Article)

Hepatocellular cancer (HCC) is one of the leading causes of mortality worldwide. Unfortunately, a limited choice of anti-cancer drugs is available for treatment, owing to their minimal efficacy and development of acquired resistance. Autophagy, a cellular survival pathway, often exhibits a pleiotropic role in HCC progression. Studies show increased autophagy in established HCC, promoting the survival of HCC cells in the tumour microenvironment. Therefore, novel anti-autophagy drugs hold promise for preventing HCC progression. Here, using a non-biased transcriptomics analysis in HepG2 cells we demonstrate the existence of an autophagy-FOXM1 nexus regulating growth in HepG2 cells. Additionally, we show that suppression of autophagy by an Unc-51 Like Autophagy Activating Kinase 1(ULK1) inhibitor not only attenuates the expression of FOXM1 and its transcriptional targets, but also has a synergistic effect on the inhibition of HepG2 growth when combined with FOXM1 inhibitors. Thus, the autophagic protein, ULK1, is a promising candidate for preventing HCC progression. Collectively, our results provide new insight into the role of autophagy in HCC growth and are a proof-of concept for combinatorial therapy using ULK1 and FOXM1 inhibitors.

Full Text

Duke Authors

Cited Authors

  • Rajak, S; Raza, S; Tewari, A; Yadav, S; Ghosh, S; Yen, PM; Sinha, RA

Published Date

  • November 19, 2020

Published In

Volume / Issue

  • 532 / 4

Start / End Page

  • 570 - 575

PubMed ID

  • 32900486

Electronic International Standard Serial Number (EISSN)

  • 1090-2104

Digital Object Identifier (DOI)

  • 10.1016/j.bbrc.2020.08.068

Language

  • eng

Conference Location

  • United States