Severe metabolic alterations in liver cancer lead to ERK pathway activation and drug resistance.

ABSTRACT:

Background

The extracellular signal-regulated kinase (ERK) pathway regulates cell growth, and is hyper-activated and associated with drug resistance in hepatocellular carcinoma (HCC). Metabolic pathways are profoundly dysregulated in HCC. Whether an altered metabolic state is linked to activated ERK pathway and drug response in HCC is unaddressed.

Methods

We deprived HCC cells of glutamine to induce metabolic alterations and performed various assays, including metabolomics (with ¹³C-glucose isotope tracing), microarray analysis, and cell proliferation assays. Glutamine-deprived cells were also treated with kinase inhibitors (e.g. Sorafenib, Erlotinib, U0126 amongst other MEK inhibitors). We performed bioinformatics analysis and stratification of HCC tumour microar

SUBMITTER: Nwosu ZC 

PROVIDER: S-EPMC7182727 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature