Crucial role of Anxa2 in cancer progression: highlights on its novel regulatory mechanism

Abstract

Anxa2 is the most studied member of the calcium-mediated phospholipid-binding protein family annexins and is a biomarker in cancers. In this review, we listed clinical findings and confirmed the value of Anxa2 in early diagnosis and prognostic prediction due to its overexpression and adverse effect on the outcome in most tumors. Anxa2 plays a pivotal role in cancer cell proliferation, migration, invasion, metastasis, and treatment resistance. Improved understanding of its cancer-promoting function might make it an ideal target for cancer therapy. Here, we systematically summarized the mechanism of Anxa2 in regulating epithelial-mesenchymal transition (EMT), cytoskeleton dynamicity, cell cycle, apoptosis, angiogenesis, and immunology by using various tumor models. These data emphasize the potential of Anxa2 for targeted intervention in tumors. Altering Anxa2 expression, neutralizing the cell surface Anxa2, or inhibiting its activation, such as through Tyr23 phosphorylation, could be considered based on the regulatory mechanism of Anxa2 in tumor progression.

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

“…49 ANXA2 has been widely involved in the variety of cell processes such as cell proliferation, differentiation, apoptosis, migration, membrane repair, as well as immunosuppression and inflammatory response, and closely associated with a poor prognosis and the disease severity in patients with these disease conditions. 50,51 2 | HOW DOES ANXA2 PARTICIPATE IN EPITHELIAL-MESENCHYMAL TRANSITION (EMT)?…”

“…Under pathological conditions, plasmin generated by ANXA2 heterotetramer converts the pro-MMP into MMP, and promotes extracellular matrix and basement membrane dissolution, as well as the release of endothelial cells and angiogenesis regulators in the matrix (such as vascular endothelial growth factor), activating the angiogenesis system and promoting angiogenesis. 31,51,86,105 Neoangiogenesis can provide necessary nutritional support for tumor growth, and at the same time, it also enables tumor cell growth and invasion. [105][106][107] Therefore, ANXA2 blockade to reduce plasmin can inhibit the neoangiogenesis and tumor growth (Figure 2).…”

“…12 Cyclin D1 is a downstream factor of C-Myc and a key promoter of cell proliferation. 51 Cyclin D1 stimulates proliferation of cancer cells by promoting the transition from G1 to S phase. 51,120 The study suggested that ANXA2 upregulation increased the expression of C-Myc and Cyclin D1 via activating the ERK1/2 signaling pathway, thereby regulating cell proliferation.…”

“…51 Cyclin D1 stimulates proliferation of cancer cells by promoting the transition from G1 to S phase. 51,120 The study suggested that ANXA2 upregulation increased the expression of C-Myc and Cyclin D1 via activating the ERK1/2 signaling pathway, thereby regulating cell proliferation. 120 Researchers found that knocking down ANXA2 with shANXA2 in human breast cancer cell lines inhibited EGF-induced phosphorylation of STAT3 and reduced Cyclin D1 levels.…”

“…146 Andersen et al proved that by binding with Toll-like receptor 2 (TLR2), ANXA2 monomer on the cell membrane induced dendritic cells to differentiate and mature, and increased the expression of CD80 and CD86, allowing foreign antigens to enter the histocompatibility complex MHC class I pathway. 49,51 C1q was the initiator of the classical complement pathway and could regulate apoptotic cells to promote phagocytosis. 147 Martin et al found that the ANXA2 monomer on the cell membrane could be used as a new ligand for the classical complement pathway promoter C1q on apoptotic cells.…”