Impact of De Novo Cholesterol Biosynthesis on the Initiation and Progression of Breast Cancer

Abstract

Cholesterol (CHOL) is a multifaceted lipid molecule. It is an essential structural component of cell membranes, where it cooperates in regulating the intracellular trafficking and signaling pathways. Additionally, it serves as a precursor for vital biomolecules, including steroid hormones, isoprenoids, vitamin D, and bile acids. Although CHOL is normally uptaken from the bloodstream, cells can synthesize it de novo in response to an increased requirement due to physiological tissue remodeling or abnormal proliferation, such as in cancer. Cumulating evidence indicated that increased CHOL biosynthesis is a common feature of breast cancer and is associated with the neoplastic transformation of normal mammary epithelial cells. After an overview of the multiple biological activities of CHOL and its derivatives, this review will address the impact of de novo CHOL production on the promotion of breast cancer with a focus on mammary stem cells. The review will also discuss the effect of de novo CHOL production on in situ and invasive carcinoma and its impact on the response to adjuvant treatment. Finally, the review will discuss the present and future therapeutic strategies to normalize CHOL biosynthesis.

PKMYT1 knockdown inhibits cholesterol biosynthesis and promotes the drug sensitivity of triple-negative breast cancer cells to atorvastatin

“…Cholesterol, a crucial element in the structure of cell membranes, plays a vital role in controlling intracellular traffic and signaling pathways. Though cells typically absorb cholesterol from the blood, they have the ability to produce cholesterol themselves when there is a greater demand caused by tissue remodeling or abnormal cell growth, such as in cases of cancer ( Coradini, 2024 ). It has been demonstrated that cholesterol biosynthesis is significantly enhanced in TNBC ( Xu et al, 2020 ).…”