Fig. 10

Illustration of potential mechanisms by which HE4 may affect cell sensitivity to Pac. Paclitaxel stabilizes the microtubule and protects it from disassembly, leading to cell cycle arrest and inhibition of cell proliferation as reflected by concomitant changes in cell cycle regulators of PCNA and p21. On the other side, HE4 may modulate cell cycle factors through its protease inhibitory action on paclitaxel-related cell cycle regulators. Alternatively, HE4 could affect other factors up- and down-stream of PCNA and p21. In any case, HE4 function may impact the cell sensitivity to paclitaxel through an action(s) related to paclitaxel, and these effects would converge to a pathway most possibly governing the cell cycle progression