Valosin-Containing Protein (VCP)/p97: A Prognostic Biomarker and Therapeutic Target in Cancer

• Published in: International journal of molecular sciences Vol. 22; no. 18; p. 10177
• Main Authors: Costantini, Susan, Capone, Francesca, Polo, Andrea, Bagnara, Palmina, Budillon, Alfredo
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 21-09-2021; MDPI
• Subjects: AAA+ ATPase; Adenosine triphosphatase; Apoptosis; Autophagy; Biomarkers; Biosynthesis; Cancer; CB-5083; Cell cycle; Cell division; Cofactors; Endoplasmic reticulum; Gene expression; Homeostasis; Kinases; Lipids; Localization; Membrane proteins; Membranes; Mitochondria; Mutation; p97; Polypeptides; prognostic biomarker; Proteins; Quality control; Review; RNA polymerase; Therapeutic applications; Ubiquitin; Valosin-containing protein; VCP
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms221810177

Valosin-containing protein (VCP)/p97, a member of the AAA+ ATPase family, is a molecular chaperone recruited to the endoplasmic reticulum (ER) membrane by binding to membrane adapters (nuclear protein localization protein 4 (NPL4), p47 and ubiquitin regulatory X (UBX) domain-containing protein 1 (UBXD1)), where it is involved in ER-associated protein degradation (ERAD). However, VCP/p97 interacts with many cofactors to participate in different cellular processes that are critical for cancer cell survival and aggressiveness. Indeed, VCP/p97 is reported to be overexpressed in many cancer types and is considered a potential cancer biomarker and therapeutic target. This review summarizes the role of VCP/p97 in different cancers and the advances in the discovery of small-molecule inhibitors with therapeutic potential, focusing on the challenges associated with cancer-related VCP mutations in the mechanisms of resistance to inhibitors.