Title:A Comprehensive Review on PCSK9 as Mechanistic Target Approach in
Cancer Therapy
Volume: 23
Issue: 1
Author(s): Amita Singh, Pranesh Kumar, Archana Bharti Sonkar, Anurag Kumar Gautam, Abhishek Verma, Biswanath Maity, Himani Tiwari, Nanda Gopal Sahoo, Amit K. Keshari, S.K. Yadav and Sudipta Saha*
Affiliation:
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raibareli Road,
Lucknow 226025, India
Keywords:
PCSK9, cancer, LDLR, JNK, NF-κВ, mitochondrial-mediated apoptotic pathway.
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.
