AQP9 and colorectal carcinoma: As a transmembrane channel, AQP9 first act as a gate to small-molecule drugs, which functionally controls 5-FU uptake and accumulation in cells; on the other hand, AQP9 may induce S-phase cell cycle arrest through activation of RAS and downstream signaling pathway, thus further increasing the cytotoxicity of S-phase-specific drug 5-FU that accumulated in CRC cells (Figure 7).