Annexin A2-mediated cancer progression and therapeutic resistance in nasopharyngeal carcinoma

Abstract

Nasopharyngeal carcinoma (NPC) is a head and neck cancer with poor clinical outcomes and insufficient treatments in Southeast Asian populations. Although concurrent chemoradiotherapy has improved recovery rates of patients, poor overall survival and low efficacy are still critical problems. To improve the therapeutic efficacy, we focused on a tumor-associated protein called Annexin A2 (ANXA2). This review summarizes the mechanisms by which ANXA2 promotes cancer progression (e.g., proliferation, migration, the epithelial-mesenchymal transition, invasion, and cancer stem cell formation) and therapeutic resistance (e.g., radiotherapy, chemotherapy, and immunotherapy). These mechanisms gave us a deeper understanding of the molecular aspects of cancer progression, and further provided us with a great opportunity to overcome therapeutic resistance of NPC and other cancers with high ANXA2 expression by developing this prospective ANXA2-targeted therapy.

Rack1 mediates tyrosine phosphorylation of Anxa2 by Src and promotes invasion and metastasis in drug-resistant breast cancer cells

“…Anxa2 overexpression promotes chemoresistance in non-small cell lung cancer, pancreatic cancer, neuroblastoma, and hepatocarcinoma [16,17,54,55]. Moreover, Anxa2 confers increased invasiveness in breast cancer (Additional file 2: Figure S5 B and C) [18,56,57]; Anxa2 knockdown also inhibits migration and invasion in nasopharyngeal carcinoma [21,22]. However, whether Anxa2 expression per se or its phosphorylated form confers the aggressive phenotype of drug-resistant cells remains unclear.…”

“…The increased expression of Anxa2 in these cells not only confers resistance to anticancer agents, but also enhances their aggressive behavior [18,21,22]. Moreover, clinical studies have shown that Anxa2 overexpression is positively correlated to poor response to anticancer agents and rapid recurrence in cancer patients who had received chemotherapy [21,[23][24][25]. This evidence suggests that Anxa2 is a key protein that links drug resistance and cancer metastasis.…”

“…In addition, a high Anxa2 level has been observed in many types of drug-resistant cells [16][17][18][19][20]. The increased expression of Anxa2 in these cells not only confers resistance to anticancer agents, but also enhances their aggressive behavior [18,21,22]. Moreover, clinical studies have shown that Anxa2 overexpression is positively correlated to poor response to anticancer agents and rapid recurrence in cancer patients who had received chemotherapy [21,[23][24][25].…”

Bioinformatics strategy for the screening of key genes to differentiate adenomyosis from endometriosis (Review)

“…gov/pubmed/) (Table II). In comparison with the genetic and proteomic data previously published for adenomyosis and (13,30), L-selectin ligand (31) and Annexin A2 (ANXA2) (32)(33)(34)(35), were considered to be target genes for adenomyosis. These previous studies revealed that, among these, 4 genes (IGF1, KISS1, NCAM1 and ANXA2) were upregulated, and 3 genes (OPN, VCAN and L-selectin ligand) were downregulated.…”

“…i) ANXA2. ANXA2 acts as a tumor-associated protein and promotes cancer proliferation, invasion, EMT and metastasis (35). ANXA2 expression has been found to be upregulated (32) and downregulated (33,34) in adenomyosis and endometriosis, respectively.…”