Annexin A2 (ANX A2): An emerging biomarker and potential therapeutic target for aggressive cancers

ANX A2 is an important member of annexin family of proteins expressed on surface of endothelial cells (ECs), macrophages, mononuclear cells and various types of cancer cells. It exhibits high affinity binding for calcium (Ca++) and phospholipids. ANX A2 plays an important role in many biological pro...

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Bibliographic Details
Published in:International journal of cancer 2019-05, Vol.144 (9), p.2074-2081
Main Author: Sharma, Mahesh C.
Format: Article
Language:English
Subjects:
Antineoplastic drugs
Antitumor agents
ANX A2
Autophagy
Calcium
Cancer
Cell activation
Cell surface
Drug development
Drug resistance
ECM
Endocytosis
Endothelial cells
Exocytosis
Extracellular matrix
Growth factors
Leukocytes (mononuclear)
Macrophages
Medical research
Metastases
Metastasis
neoangiogenesis
Phagocytosis
Phospholipids
Plasmin
Proteins
Proteolysis
Serine
Serine proteinase
t-Plasminogen activator
Therapeutic applications
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Summary:ANX A2 is an important member of annexin family of proteins expressed on surface of endothelial cells (ECs), macrophages, mononuclear cells and various types of cancer cells. It exhibits high affinity binding for calcium (Ca++) and phospholipids. ANX A2 plays an important role in many biological processes such as endocytosis, exocytosis, autophagy, cell–cell communications and biochemical activation of plasminogen. On the cell surface ANX A2 organizes the assembly of plasminogen (PLG) and tissue plasminogen activator (tPA) for efficient conversion of PLG to plasmin, a serine protease. Proteolytic activity of plasmin is required for activation of inactive pro‐metalloproteases (pro‐MMPs) and latent growth factors for their biological actions. These activation steps are critical for degradation of extracellular matrix (ECM) and basement proteins (BM) for cancer cell invasion and metastasis. Increased expression of ANX A2 protein/gene has been correlated with invasion and metastasis in a variety of human cancers. Moreover, clinical studies have positively correlated ANX A2 protein expression with aggressive cancers and with resistance to anticancer drugs, shorter disease‐free survival (DFS), and worse overall survival (OS). The mechanism(s) by which ANX A2 regulates cancer invasion and metastasis are beginning to emerge. Investigators used various technologies to target ANX A2 in preclinical model of human cancers and demonstrated exciting results. In this review article, we analyzed existing literature concurrent with our own findings and provided a critical overview of ANX A2‐dependent mechanism(s) of cancer invasion and metastasis.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.31817