Cholesterol Metabolism and Acyltransferase Dynamics in Cancer Systems

Cancer cells frequently reprogramme cholesterol metabolism to support rapid proliferation, membrane biogenesis and signalling functions. Central to this reprogramming is the balance between free cholesterol and its esterified form, a reaction catalysed by acyltransferases in the endoplasmic reticulum. Acyl-CoA:cholesterol acyltransferase (ACAT) isoenzymes and sterol O-acyltransferase 1 (SOAT1) govern the formation of cholesteryl esters, directing lipid storage into cytoplasmic droplets. Enhanced cholesterol esterification contributes to endoplasmic reticulum stress, activation of survival pathways and epithelial–mesenchymal transition, thereby facilitating invasion and metastasis. Conversely, accumulation of free cholesterol can trigger apoptotic cascades. Detailed structural insights into acyltransferase active sites have opened routes for rational inhibitor design. Furthermore, inflammatory and oncogenic signalling networks, notably nuclear factor-κB, create a positive feedback that amplifies cholesterol accumulation and tumour progression. Understanding the interplay between cholesterol flux, acyltransferase dynamics and tumour microenvironment is pivotal for developing metabolic interventions and targeted therapeutics in diverse cancer types.

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Cholesterol Metabolism and Acyltransferase Dynamics in Cancer Systems publication trend

The graph below shows the total number of articles in cholesterol metabolism and acyltransferase dynamics in cancer systems across all publications each year (not limited to Nature Index journals).

Technical terms

Acyl-CoA:cholesterol acyltransferase (ACAT): Endoplasmic reticulum enzyme family that esterifies free cholesterol with fatty acyl-CoA for storage as cholesteryl esters.

Sterol O-acyltransferase 1 (SOAT1): A membrane-bound O-acyltransferase that catalyses the formation of cholesteryl esters and regulates cholesterol homeostasis.

Cholesterol esterification: Biochemical process converting free cholesterol into cholesteryl esters, facilitating lipid droplet formation and intracellular storage.

Epithelial–mesenchymal transition (EMT): A cellular programme in which epithelial cells acquire mesenchymal traits, enhancing motility and invasive capacity.

NF-κB signalling: A transcriptional pathway activated by inflammatory stimuli that regulates genes controlling cell survival, proliferation and lipid metabolism.

References

1. SOAT1 regulates cholesterol metabolism to induce EMT in hepatocellular carcinoma. Cell Death & Disease (2024).
2. Abrogating cholesterol esterification suppresses growth and metastasis of pancreatic cancer. Oncogene (2016).
3. Pro-inflammation NF-κB signaling triggers a positive feedback via enhancing cholesterol accumulation in liver cancer cells. Journal of Experimental & Clinical Cancer Research (2017).
4. Cell Toxicity Induced by Inhibition of Acyl Coenzyme A:Cholesterol Acyltransferase and Accumulation of Unesterified Cholesterol ∗. Journal of Biological Chemistry (1995).
5. Structural insights into the inhibition mechanism of human sterol O-acyltransferase 1 by a competitive inhibitor. Nature Communications (2020).