Annexin A2: The diversity of pathological effects in tumorigenesis and immune response

Abstract

Annexin A2 (ANXA2) is widely used as a marker in a variety of tumors. By regulating multiple signal pathways, ANXA2 promotes the epithelial‐mesenchymal transition, which can cause tumorigenesis and accelerate thymus degeneration. The elevated ANXA2 heterotetramer facilitates the production of plasmin, which participates in pathophysiologic processes such as tumor cell invasion and metastasis, bleeding diseases, angiogenesis, inducing the expression of inflammatory factors. In addition, the ANXA2 on the cell membrane mediates immune response via its interaction with surface proteins of pathogens, C1q, toll‐like receptor 2, anti‐dsDNA antibodies and immunoglobulins. Nuclear ANXA2 plays a role as part of a primer recognition protein complex that enhances DNA synthesis and cells proliferation by acting on the G1‐S phase of the cell. ANXA2 reduction leads to the inhibition of invasion and metastasis in multiple tumor cells, bleeding complications in acute promyelocytic leukemia, retinal angiogenesis, autoimmunity response and tumor drug resistance. In this review, we provide an update on the pathological effects of ANXA2 in both tumorigenesis and the immune response. We highlight ANXA2 as a critical protein in numerous malignancies and the immune host response.

Urine proteomic analysis of the rat e-cigarette model

“…Currently, the physiological role of OBPs is not fully understood [35] , and perhaps the urine proteome can play a role in exploring the specific mechanism of action of OBPs. Annexin A2 is widely used as a marker for a variety of tumors [36] . In addition, László ZI et al showed that neurocadherin is one of the most important cell adhesion molecules during brain development and plays an important role in neuronal formation, neuronal proliferation, differentiation and migration, axonal guidance, synaptogenesis and synaptic maintenance [37] .…”

Higher Expression of Annexin A2 in Metastatic Bladder Urothelial Carcinoma Promotes Migration and Invasion

“…Annexins display different expression patterns in bladder cancer and play an essential role in the pathogenesis by triggering various downstream signaling pathways and functional regulatory effects [ 19 , 20 , 43 , 44 , 45 , 46 , 47 , 48 ]. Increasing evidence indicates that AnxA2 is upregulated in several types of human cancer [ 13 , 17 , 21 , 22 , 24 , 26 , 27 , 28 , 29 ]. Annexin A2 is a potential biomarker for predicting drug resistance and recurrence of bladder cancers [ 19 , 20 ].…”

“…Upregulation of AnxA2 has been observed in gastric cancer, endometrial cancer, pancreatic ductal adenocarcinoma, hepatocellular carcinoma, breast cancer, kidney renal clear cell carcinoma, high-grade prostate cancer, and glioblastoma. It has a significant correlation with advanced stage and unfavorable prognosis [ 13 , 17 , 21 , 22 , 24 , 26 , 27 , 28 , 29 ]. Previous studies suggested that AnxA2 was upregulated in bladder urothelial carcinoma tumor tissues and associated with lymph node metastasis and distant metastasis [ 19 , 20 ].…”

“…AnxA2 exists as a monomer in the cytosol and a heterotetramer when linked to the cell membrane [ 12 ]. The heterotetrameric form consists of two AnxA2 monomers and two subunits of p11 and is involved in proliferation, migration, adhesion, invasion, resistance to chemotherapy, angiogenesis, plasmin generation, and ion channel conductance [ 11 , 12 , 13 , 14 , 17 , 18 , 19 , 20 , 21 ]. Several studies have shown that the AnxA2 expression is correlated with high tumor grade and stage and poor survival of cancer patients [ 13 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ].…”

ANXA2 is a potential biomarker for cancer prognosis and immune infiltration: A systematic pan-cancer analysis

“…Annexin A2 (ANXA2) is a calcium-dependent phospholipid binding protein and regulates cellular growth ( Hajjar and Krishnan, 1999 ; Wang and Lin, 2014 ). ANXA2 is involved in various pathophysiological processes, including epithelial-mesenchymal transition, fibrinolysis and cancer drug resistance ( Wang et al, 2019 ; Huang et al, 2022 ). In vitro , ANXA2 promoted migration and invasion of esophageal squamous carcinoma cells by activating the MYC-HIF1A-VEGF signaling cascade ( Wu et al, 2019 ).…”