Futhermore, these observations suggest that unlike the possible direct effect of HMGB1 on the expansion of CK19-positive or SOX9-positive ductual cells2, the tumor-promoting effect of HMGB1 may not be mediated by a direct effect on the autophagy-deficient hepatocytes, but possibly by an indirect effect through other RAGE-expressing cells, such as the Kupffer’s cells, which could then alter the microenvironment to facilitate tumor development. The gene discussed is HMGB1; the disease is neoplasm.