In addition to modulating the TGF-β pathway by targeting SMURF2 [12], NS3 can also enhance cancer cell invasion by activating matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2) through the ERK/p38/NF-κB signal cascade [35], and interact with p53 to inhibit p53-dependent transcription [30]. Here, SMURF2 is linked to cancer.