F11 Receptor/Junctional Adhesion Molecule-A: a novel therapeutic target in breast cancer.

Breast cancer (BC) is the most common cancer and the leading cause of cancer death among women worldwide. Its treatment is often ineffective due to metastasis in all BC subtypes and resistance to targeted therapy in HER2-positive breast cancer (HER2+ BC). On the other hand, the lack of traditional cell surface markers for molecularly targeted therapy in triple-negative breast cancer (TNBC) limits its treatment to conventional chemotherapy. Therefore, there is an urgent need to identify new molecular targets for BC therapy. The endothelial barrier, maintained by several types of cell junctions, including tight junctions (TJs), is loosened by cancer cells during the metastasis-linked processes. Cancer cells disrupt TJs in the endothelial wall of blood vessels and new TJs are formed between endothelial cells and cancer cells, leading to metastasis. The level of a TJ protein, F11 platelet receptor aka junctional adhesion molecule-A (F11R/JAM-A), is abnormal in most types of cancer, particularly in BC. The idea of targeting the F11R/JAM-A protein for BC treatment arose from the discovery that overexpression of the miR-145 microRNA in BC cells reduced F11R/JAM-A level and decreased cell migration. This observation was confirmed by subsequent studies, which supported the importance of F11R/JAM-A in cancer progression, particularly in BC. In this review, F11R/JAM-A is characterized as a molecular target for BC therapy. Particular attention was paid to peptide antagonists of F11R/JAM-A, that appear to be promising candidates for anticancer drugs.