SREBP-1c as a molecular bridge between lipogenesis and cell cycle progression of clear cell renal carcinoma.

Gautam Sethi,Alan Prem Kumar,Muthu K Shanmugam

doi:10.1042/bsr20171270

Abstract

Sterol regulatory element binding protein 1c (SREBP-1c) promotes lipogenesis and tumor growth in various cancers. It is well known that clear cell renal cell carcinoma (ccRCC), a major subtype of the kidney cancers, exhibits elevated lipid accumulation. However, it has not been fully understood how lipid metabolism might be associated with cell cycle regulation in ccRCC. In a recent issue, Lee et al. (Molecular and Cellular Biology (2017) pii: MCB.00265-17) demonstrate that SREBP-1c is up-regulated in ccRCC by ring finger protein 20 (RNF20) down-regulation, leading to aberrant lipid storage and pituitary tumor transforming gene 1 (PTTG1)-dependent cell cycle progression. These findings suggest that SREBP-1c serves as a molecular bridge between lipid metabolism and cell cycle control in ccRCC tumorigenesis.

Highlights

Metabolic reprogramming is one of the hallmarks in most cancer cells
This study demonstrates the hypoxia-inducible factor (HIF)-2α/Perilipin 2 (PLIN2) axis maintains lipid droplets to protect against endoplasmic reticulum (ER) stress in clear cell renal cell carcinoma (ccRCC), the underlying mechanisms that are involved in ectopic lipid accumulation and cell cycle regulation in ccRCC have not been fully elucidated
The Cancer Genome Atlas (TCGA) reveals that mRNA levels of Sterol regulatory element binding proteins (SREBPs)-1c and lipogenic genes are up-regulated in ccRCC patients, which is accompanied with advanced tumor stages and poor survival [10]

Summary

Introduction

Metabolic reprogramming is one of the hallmarks in most cancer cells. Tumor cells exhibit enhanced aerobic glycolysis and elevated lipogenesis to supply energy and building blocks, which are required for excessive cell growth [1]. RNF20 represses cell cycle progression by modulating pituitary tumor transforming gene 1 (PTTG1) as a novel SREBP-1c target gene.

Results

Conclusion