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.

Effect of High-Quality Nursing Intervention on the Quality of Life and Psychological State of Tumor Patients Undergoing First Chemotherapy

“…Malignant tumor considerably threatens the human health and is regarded as a global health concern. The WHO survey shows that about 30% of cancer patients have missed the optimal treatment time at the time of diagnosis, and chemotherapy remains unavailable to alleviate the disease [ 9 , 10 ]. At present, chemotherapy is the mainstay to prolong the life of patients with malignant tumors, but chemotherapy is associated with multiple side effects.…”

Immunoexpression of p62/SQSTM1/Sequestosome‑1 in human primary and recurrent IDH1/2 wild‑type glioblastoma: A pilot study

“…Moreover, p62 overexpression has been reported also in glioma cell lines and no difference in p62 expression between IDH wild-type or IDH mutated groups was reported, suggesting that p62 function may be considered independent of IDH status ( 15 , 33 ). Consequently, it can be argued that p62 overexpression stimulates the classical autophagic pathway, allowing GBM cell survival by antagonizing apoptosis and producing drug resistance to proteasome inhibitors ( 17 , 50 , 51 ). Alternatively, an accumulation of the autophagy substrate p62 may reveal a defective process that cannot degrade its substrates.…”

“…Among the ATGs, a multifunctional protein considered autophagy adaptor is represented by p62, also named sequestosome 1 (SQSTM 1) (15,16); in particular, this protein may directly interact with microtubule-associated protein light chain 3 (LC3), and further, it may be specifically degraded by autophagy (15). Contrastingly, a defective autophagic phenomenon may produce a p62 upregulation in human tumors (17,18). Some reports have documented an evident p62 expression in pancreatic, hepatocellular, mammary, and oral squamous carcinomas, in which aggressive clinicopathological features and poor prognosis have been referred (16)(17)(18)(19)(20).…”

“…Contrastingly, a defective autophagic phenomenon may produce a p62 upregulation in human tumors (17,18). Some reports have documented an evident p62 expression in pancreatic, hepatocellular, mammary, and oral squamous carcinomas, in which aggressive clinicopathological features and poor prognosis have been referred (16)(17)(18)(19)(20).…”

Tackling the Behavior of Cancer Cells: Molecular Bases for Repurposing Antipsychotic Drugs in the Treatment of Glioblastoma

“…It acts as both a pro-oncogenic and a tumor suppressor protein by affecting proliferation, invasion, and response to chemotherapy and RT. Furthermore, p62 participates in activating or inactivating signaling pathways related to the tumor microenvironment and influencing EMT [ 132 ].…”