Cholesterol homeostasis and cancer: a new perspective on the low-density lipoprotein receptor.

Cell Oncol (Dordr)

Laboratory of Stem Cell Regulation With Chinese Medicine and Its Application, Hunan University of Chinese Medicine, Changsha, 410208, China.

Published: October 2022

AI Article Synopsis

  • Disturbances in cholesterol balance are linked to cancer, with cholesterol essential for various cancer cell functions, and the LDLR playing a key role in regulating cholesterol uptake and homeostasis.* -
  • LDLR is often overexpressed in many cancers (e.g., colon, lung, breast), impacts multiple signaling pathways, and may serve as an independent prognostic factor for certain cancer types, although its role in prostate cancer is still debated.* -
  • Understanding the dysregulation of LDLR presents new therapeutic opportunities, as targeting LDLR could lead to innovative cancer treatments by restoring cholesterol homeostasis and potentially improving patient outcomes.*

Article Abstract

Background: Disturbance of cholesterol homeostasis is considered as one of the manifestations of cancer. Cholesterol plays an essential role in the pleiotropic functions of cancer cells, including mediating membrane trafficking, intracellular signal transduction, and production of hormones and steroids. As a single transmembrane receptor, the low-density lipoprotein receptor (LDLR) can participate in intracellular cholesterol uptake and regulate cholesterol homeostasis. It has recently been found that LDLR is aberrantly expressed in a broad range of cancers, including colon cancer, prostate cancer, lung cancer, breast cancer and liver cancer. LDLR has also been found to be involved in various signaling pathways, such as the MAPK, NF-κB and PI3K/Akt signaling pathways, which affect cancer cells and their surrounding microenvironment. Moreover, LDLR may serve as an independent prognostic factor for lung cancer, breast cancer and pancreatic cancer, and is closely related to the survival of cancer patients. However, the role of LDLR in some cancers, such as prostate cancer, remains controversial. This may be due to the lack of normal feedback regulation of LDLR expression in cancer cells and the severe imbalance between LDLR-mediated cholesterol uptake and de novo biosynthesis of cholesterol.

Conclusions: The imbalance of cholesterol homeostasis caused by abnormal LDLR expression provides new therapeutic opportunities for cancer. LDLR interferes with the occurrence and development of cancer by modulating cholesterol homeostasis and may become a novel target for the development of anti-cancer drugs. Herein, we systematically review the contribution of LDLR to cancer progression, especially its dysregulation and underlying mechanism in various malignancies. Besides, potential targeting and immunotherapeutic options are proposed.

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Source
http://dx.doi.org/10.1007/s13402-022-00694-5DOI Listing

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