Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 18, Pages -Publisher
MDPI
DOI: 10.3390/ijms221810177
Keywords
VCP; p97; AAA plus ATPase; cancer; prognostic biomarker; CB-5083
Funding
- Italian Ministry of Health - Ricerca Corrente Funds-Istituto NazionaleTumori G. Pascale-Progetti M3/6 and M2/5
- POR CAMPANIA FESR [B61G18000470007]
- FIRC-AIRC Fellowship-Italy [24190]
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The review outlines the role of VCP/p97 in different cancers and its potential as a cancer biomarker and therapeutic target, while also addressing the challenges posed by VCP mutations in resistance to inhibitors.
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.
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