A Novel Fifth Hexokinase, HKDC1, Mediates NASH-Induced Liver Cancer Through Modulating Mitochondrial Function
Abstract
Cancer cells dynamically undergo metabolic reprogramming to enhance glucose metabolism which is essential for both energy production and providing building blocks. The role of the mitochondria has independently emerged as a key regulator of metabolic reprogramming due to their role in sensing and controlling nutrient flux and metabolism. The effect of hexokinase (HK) interaction with the mitochondria has been documented in cancer; however, the exact mechanisms are not well established. Recently a 5th HK, hexokinase domain containing 1 (HKDC1) has been shown to be significantly overexpressed in hepatocellular carcinoma (HCC) to a greater degree than other HKs. Non-alcoholic steatohepatitis (NASH) is an independent risk factor for the development of HCC particularly due to its prevalence in developing countries. The goal of this proposal is to mechanistically investigate how HKDC1 could be a link between the progression of NASH to HCC via its role at the mitochondria. Our key data (via knockout and overexpression) shows that 1) HKDC1 has a role in HCC development and progression and 2) its interaction with the mitochondria (via N-terminal) is essential for its role in HCC progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2021
- Accession Number
- AD1152665
Entities
People
- Wasim Khan
Organizations
- University of Illinois Urbana–Champaign