A schematic representation of a proposed mechanism involved in CypA-mediated cell proliferation in CCA. CypA is upregulated in CCA cells, and several carcinogenic factors such as HIF-1a and p53 may regulate CypA expression. Unusual high CypA protein level may lead to sustained activation of ERK1/2 and NF-kB through direct or indirect mechanisms, which in turn activate cell survival, proliferation, and tumor progression. CypA may be secreted from the cells and act as an autocrine/paracrine growth factor via interacting with its membrane receptor CD147. Using specific inhibitor against CypA or against CypA/CD147 binding may inhibit CCA cell proliferation and tumor progression.