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Updated: Oct 11, 2025
A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
Published on: August 28, 2018
A Comprehensive Review on PCSK9 as Mechanistic Target Approach in Cancer Therapy
Amita Singh1, Pranesh Kumar1,2, Archana Bharti Sonkar1
1Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raibareli Road, Lucknow 226025, India.
Abstract:
PCSK9 is a strongly expressed protein in the liver and brain that binds to the LDLR and regulates cholesterol in the liver effectively. Other receptors with which it interacts include VLDLR, LRP1, ApoER2, and OLR1. PCSK9 gain-of-function results in lysosomal degradation of these receptors, which may result in hyperlipidemia. PCSK9 deficiency results in a lower amount of cholesterol, which reduces cholesterol's accessibility to cancer cells. PCSK9 regulates several proteins and signaling pathways in cancer, including JNK, NF-κВ, and the mitochondrial-mediated apoptotic pathway. In the liver, breast, lungs, and colon tissue, PCSK9 initiates and facilitates cancer development, while in prostate cancer cells, it induces apoptosis. PCSK9 has a significant impact on brain cancer, promoting cancer cell survival by manipulating the mitochondrial apoptotic pathway and exhibiting apoptotic activity in neurons by influencing the NF-κВ, JNK, and caspase-dependent pathways. The PCSK9 impact in cancer at different organs is explored in this study, as well as the targeted signaling mechanisms involved in cancer growth. As a result, these signaling mechanisms may be aimed for the development and exploration of anti-cancer drugs in the immediate future.
Insights
Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a dual role in cancer, promoting growth in some tissues while inducing apoptosis in others. Targeting PCSK9-related signaling pathways may offer new anti-cancer drug development strategies.
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of cholesterol metabolism through its interaction with the low-density lipoprotein receptor (LDLR).
- PCSK9's role extends beyond lipid regulation, influencing various cellular processes relevant to cancer development and progression.
- Dysregulation of PCSK9 can lead to hyperlipidemia and impacts cellular signaling pathways involved in cancer.
Approach:
- This study explores the multifaceted impact of PCSK9 on cancer across different organs.
- It investigates the specific signaling mechanisms, including JNK, NF-κB, and mitochondrial apoptotic pathways, modulated by PCSK9 in cancer cells.
- The research examines PCSK9's contrasting effects, such as promoting cancer in liver and breast tissues while inducing apoptosis in prostate cancer and neurons.
Key Points:
- PCSK9 influences cancer development in liver, breast, lung, and colon tissues.
- In prostate cancer and neurons, PCSK9 exhibits pro-apoptotic activity.
- PCSK9 manipulates mitochondrial-mediated apoptosis and NF-κB/JNK pathways, impacting cancer cell survival and neuronal apoptosis.
Conclusions:
- PCSK9 demonstrates organ-specific roles in cancer, acting as a facilitator in some and an inducer of apoptosis in others.
- The study highlights PCSK9's significant impact on brain cancer, promoting cell survival.
- Targeting PCSK9-associated signaling pathways presents a promising avenue for future anti-cancer drug development.
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