Phosphorlyation of Annexin A2 is essential for its association with exosomes and for migration, invasion and proliferation in triple negative breast cancer

Exosomes are membrane enclosed small vesicles that range from 40-120 nm in size and participate in cell-cell communication by transferring proteins to other cells. Annexin A2 (AnxA2), a calcium-dependent phospholipid binding protein, is present on the surface of the exosomes. AnxA2 phosphorylation plays an essential role in many physiological conditions by forming a heterotetrameric complex with p11 or S100A10 on the cell surface. We demonstrate here that the phosphorylation at Tyrosine (Tyr)-23 in the N-terminal region of AnxA2 is consequential for its association with the cell surface. This association increases the migratory, invasive and proliferative capacity of MDA-MB-231 triple negative breast cancer (TNBC) cells. An increase in cell surface AnxA2 further leads to a stronger association of AnxA2 with the exosomal surface. We also demonstrate that AnxA2 enriched exosomes promote proliferative and invasive characteristics of a different recipient cell [CAL (Centre Antoine Lacassagne) - 148]. These results demonstrate that Tyr23 phosphorylation of AnxA2 is pivotal for its association with exosomes and for imparting more malignant characteristics to the other breast cancer cells. Thus, AnxA2 could be used as a targeting approach for developing a treatment of TNBC.