Proprotein convertase subtilisin/kexin type 9 (PCSK9): A potential multifaceted player in cancer

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a novel pharmacological target for hypercholesterolemia and associated cardiovascular diseases owing to its function to mediate the degradation of low-density lipoprotein receptor (LDLR). Findings over the past two decades have identified novel binding partners and cellular functions of PCSK9. Notably, PCSK9 is aberrantly expressed in a broad spectrum of cancers and apparently contributes to disease prognosis, indicating that PCSK9 could be a valuable cancer biomarker. Experimental studies demonstrate the contribution of PCSK9 in various aspects of cancer, including cell proliferation, apoptosis, invasion, metastasis, anti-tumor immunity and radioresistance, strengthening the idea that PCSK9 could be a promising therapeutic target. Here, we comprehensively review the involvement of PCSK9 in cancer, summarizing its aberrant expression, association with disease prognosis, biological functions and underlying mechanisms in various malignancies. Besides, we highlight the potential of PCSK9 as a future therapeutic target in personalized cancer medicine.