The SLIT/ROBO Pathway in Liver Fibrosis and Cancer

Liver fibrosis is a common outcome of most chronic liver insults/injuries that can develop into an irreversible process of cirrhosis and, eventually, liver cancer. In recent years, there has been significant progress in basic and clinical research on liver cancer, leading to the identification of various signaling pathways involved in tumorigenesis and disease progression. Slit glycoprotein (SLIT)1, SLIT2, and SLIT3 are secreted members of a protein family that accelerate positional interactions between cells and their environment during development. These proteins signal through Roundabout receptor (ROBO) receptors (ROBO1, ROBO2, ROBO3, and ROBO4) to achieve their cellular effects. The SLIT and ROBO signaling pathway acts as a neural targeting factor regulating axon guidance, neuronal migration, and axonal remnants in the nervous system. Recent findings suggest that various tumor cells differ in SLIT/ROBO signaling levels and show varying degrees of expression patterns during tumor angiogenesis, cell invasion, metastasis, and infiltration. Emerging roles of the SLIT and ROBO axon-guidance molecules have been discovered in liver fibrosis and cancer development. Herein, we examined the expression patterns of SLIT and ROBO proteins in normal adult livers and two types of liver cancers: hepatocellular carcinoma and cholangiocarcinoma. This review also summarizes the potential therapeutics of this pathway for anti-fibrosis and anti-cancer drug development.

Automated summary

Liver fibrosis is a common consequence of chronic liver damage and can progress to cirrhosis and liver cancer. Recent research has identified signaling pathways, such as the SLIT/ROBO pathway, involved in tumor development and progression. SLIT and ROBO proteins play important roles in axon guidance and have been found to have emerging roles in liver fibrosis and cancer development. The expression patterns of these proteins in normal adult livers and different types of liver cancer have been examined, and their potential therapeutic implications have been reviewed for anti-fibrosis and anti-cancer drug development.