The Role of Annexin A2 in Tumorigenesis and Cancer Progression

Abstract

Annexin A2 is a calcium-dependent, phospholipid-binding protein found on various cell types. It is up-regulated in various tumor types and plays multiple roles in regulating cellular functions, including angiogenesis, proliferation, apoptosis, cell migration, invasion and adhesion. Annexin A2 binds with plasminogen and tissue plasminogen activator on the cell surface, which leads to the conversion of plasminogen to plasmin. Plasmin is a serine protease which plays a key role in the activation of metalloproteinases and degradation of extracellular matrix components essential for metastatic progression. We have recently found that both annexin A2 and plasmin are increased in conditioned media of co cultured ovarian cancer and peritoneal cells. Our studies suggest that annexin A2 is part of a tumor-host signal pathway between ovarian cancer and peritoneal cells which promotes ovarian cancer metastasis. Accumulating evidence suggest that interactions between annexin A2 and its binding proteins play an important role in the tumor microenvironment and act together to enhance cancer metastasis. This article reviews the current knowledge on the biological role of annexin A2 and its binding proteins in solid malignancies including ovarian cancer.

WOMEN IN CANCER THEMATIC REVIEW: Ovarian cancer–peritoneal cell interactions promote extracellular matrix processing

“…Overexpression of annexin A2 has been demonstrated in several cancer types such as breast, pancreas, colorectal and prostate cancer (reviewed in Lokman et al 2011). Annexin A2 mRNA is upregulated 3-fold in metastatic ovarian cancer tissues compared with that in normal ovarian tissue (Tchagang et al 2008).…”

S100 and annexin proteins identify cell membrane damage as the Achilles heel of metastatic cancer cells

“…As discussed above members of the annexin family -annexin A1, A2, A5 and A6 have already been implicated in PMR and over expression of some of these annexins is directly correlated with aggressive clinical stage in colorectal, pancreatic and brain tumors and linked to metastatic progression. 78 Further, changes in annexin A3 and A4 expression has been associated with chemo resistance in ovarian cancer cells. 79,80 These findings make a case for a potential therapeutic approach against tumor metastasis that could involve targeting PMR by regulating expression of specific annexins.…”

Role of Annexin A2 in the EGF-induced epithelial-mesenchymal transition in human CaSki cells

“…ANXA2 has been demonstrated to be a co-receptor for both plasminogen and tissue-type plasminogen activator, which cleaves inactive plasminogen to yield the active serine proteinase, plasmin (12,13). Subsequent studies elucidated that the conversion of plasminogen to plasmin is induced by ANXA2 promoting metastasis, which leads to the activation of metalloproteinases, degradation of extracellular matrix components, and promotion of neoangiogenesis (14)(15)(16)(17). However, the underlying mechanisms of ANXA2 and EMT remain obscure.…”