Sequestosome 1/p62: A multitasker in the regulation of malignant tumor aggression (Review)

Abstract

Sequestosome 1 (SQSTM1)/p62 is an adapter protein mainly involved in the transportation, degradation and destruction of various proteins that cooperates with components of autophagy and the ubiquitin-proteasome degradation pathway. Numerous studies have shown that SQSTM1/p62 functions at multiple levels, including involvement in genetic stability or modification, post-transcriptional regulation and protein function. As a result, SQSTM1/p62 is a versatile protein that is a critical core regulator of tumor cell genetic stability, autophagy, apoptosis and other forms of cell death, malignant growth, proliferation, migration, invasion, metastasis and chemoradiotherapeutic response, and an indicator of patient prognosis. SQSTM1/p62 regulates these processes via its distinct molecular structure, through which it participates in a variety of activating or inactivating tumor-related and tumor microenvironment-related signaling pathways, particularly positive feedback loops and epithelial-mesenchymal transition-related pathways. Therefore, functioning as a proto-oncogene or tumor suppressor gene in various types of cancer and tumor-associated microenvironments, SQSTM1/p62 is capable of promoting or retarding malignant tumor aggression, giving rise to immeasurable effects on tumor occurrence and development, and on patient treatment and prognosis.