Linking chronic inflammation with tumor suppressor gene inactivation in liver cancer (B01)

• Subject Area: Pathology
• Term: from 2017 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 314905040

Project B01 (Rössler; Linking chronic inflammation with tumor suppressor gene inactivation in liver cancer) has established tumor suppressor cooperation in hepatocarcinogenesis by establishing that the frequent loss of chromosome 8p in HCCs leads to loss of two new tumor suppressors, SORBS3 and SH2D4A. Both suppressors collaborate in inhibition of the IL-6 signalling pathway, thus blocking its proinflammatory and protumorigenic effect. Some of the SH2D4A functions appear to be mediated by the mitochondrial protein prohibitin. Having identified genes that are essential for HCCs with loss of (PARD3, PARD6B) and wt chromosome 8p (FOXM1) in the upcoming funding period B01 will functionally dissect these genes and by using engineered chromosome 8p deleted and corresponding wildtype cells will identify further genes essential in HCCs with chromosome 8p deletion under inflammatory conditions (STAT3 activation).

• DFG Programme: CRC/Transregios
• Subproject of: TRR 209: Liver Cancer - New mechanistic and therapeutic concepts in a solid tumor model
• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Project Head: Professorin Dr. Stephanie Rössler