Fig. 2.

PLAC1 expression and function in placenta and cancer, PLAC1 is expressed by cytotrophoblasts (CTB), syncytiotrophoblasts (STB) and extravillous trophoblasts (EVT) and is associated with cell proliferation, differentiation and migration. PLAC1 is known to play a key role in placental development (a). PLAC1 is also re-expressed in several solid tumors and in most human cancer cell lines and promotes cancer cell proliferation. Expression of PLAC1 is also a triggering factor for enhanced migration of cancer cells that have undergone epithelial-mesenchymal transition (EMT) process through downregulation of E-cadherin and upregulation of vimentin (b). PLAC1 blocking by specific antibodies or silencing by RNA interference leads to cell cycle arrest in cancer cells through AKT and reduction of phosphorylated protein kinase B (PKB) and cyclin D1 levels which eventually leads to cell cycle arrest (c). PLAC1 expression in cancer cells induces cellular and humoral immune responses. Antigen-presenting cells (APC) endocytose cancer apoptotic bodies and present PLAC1-derived peptides to T cells which subsequently leads to induction of PLAC1-specific cytotoxic T cells (CTL) and antibody responses. CTLs kill PLAC1⁺ cancer cells by releasing cytotoxic lytic granules and anti-PLAC1 antibodies impair cancer cell proliferation and induce their apoptosis. It is, however, not clear to what extent anti-PLAC1 immune responses are effective in cancer control in vivo (d)