Figure 2

Xmrk signaling in the zebrafish hepatocellular carcinoma model. In transgenic zebrafish models of HCC, Xmrk signals through kinases and transcription factors that modulate liver cancer progression. PI3K activation may modulate apoptosis through the mechanistic target of rapamycin (mTOR), although mTOR expression may be decreased in HCC, making its effect on apoptosis uncertain. STAT5 signaling can promote proliferation, as does MAPK via activation of extracellular signal-regulated kinases (ERK). MAPK also has a dual role in signaling through the transcription factors, Snail and Slug, to inhibit E-cadherin activity. The formation of focal adhesions is increased through a pathway that is currently uncharacterized. Xmrk is also associated with increased expression of the tumor suppressor, p53, and the Fas receptor (FasR), which regulates apoptosis during HCC, but the details of their associated signaling mechanisms are not currently understood.