Epigenetic regulation of esophageal cancer


Project Summary

Esophageal cancers still represent a major challenge in interdisciplinary oncology. This project explores the epigenetic regulation of oesophageal cancers with respect to its pathobiology and therapeutic potential. We shall evaluate how histone modifiers guide squamous to intestinal cell differentiation in the development of oesophageal adenocarcinomas and establish in a genome-wide approach patterns of histone marks, transcriptomes, and mutational profiles. This project aims to validate epigenetic inhibitors for oesophageal cancer in a preclinical setting.

Selected project-relevant publications

  • Roatsch M., Hoffmann I., Abboud M.I., Hancock R.L., Tarhonskaya H., Hsu K.F., Wilkins S.E., Yeh T.L., Lippl K., Serrer K., Moneke I., Ahrens T.D., Robaa D., Wenzler S., Barthes N.P.F., Franz H., Sippl W., Lassmann S., Diederichs S., Schleicher E., Schofield C.J., Kawamura A., Schule R. and Jung M. (2019) The Clinically Used Iron Chelator Deferasirox Is an Inhibitor of Epigenetic JumonjiC Domain-Containing Histone Demethylases. ACS Chem Biol, doi: 10.1021/acschembio.9b00289.
  • Geissler A.L., Geissler M., Kottmann D., Lutz L., Fichter C.D., Fritsch R., Weddeling B., Makowiec F., Werner M. and Lassmann S. (2017) ATM mutations and E-cadherin expression define sensitivity to EGFR-targeted therapy in colorectal cancer. Oncotarget 8, 17164-17190.
  • Ahrens T.D., Lutz L., Lassmann S. and Werner M. (2017) Turning Skyscrapers into Town Houses: Insights into Barrett’s Esophagus. Pathobiology 84, 87-98.
  • Lutz L., Fitzner I.C., Ahrens T., Geissler A.L., Makowiec F., Hopt U.T., Bogatyreva L., Hauschke D., Werner M. and Lassmann S. (2016) Histone modifiers and marks define heterogeneous groups of colorectal carcinomas and affect responses to HDAC inhibitors in vitro. Am J Cancer Res 6, 664-676.
  • Ahrens T.D., Timme S., Ostendorp J., Bogatyreva L., Hoeppner J., Hopt U.T., Hauschke D., Werner M. and Lassmann S. (2016) Response of esophageal cancer cells to epigenetic inhibitors is mediated via altered thioredoxin activity. Lab Invest 96, 307-316.
  • Sijare F., Geissler A.L., Fichter C.D., Hergeth S.P., Bogatyreva L., Hauschke D., Schneider R., Werner M. and Lassmann S. (2015) Aurora B expression and histone variant H1.4S27 phosphorylation are no longer coordinated during metaphase in aneuploid colorectal carcinomas. Virchows Arch 466, 503-515.
  • Ahrens T.D., Timme S., Hoeppner J., Ostendorp J., Hembach S., Follo M., Hopt U.T., Werner M., Busch H., Boerries M. and Lassmann S. (2015) Selective inhibition of esophageal cancer cells by combination of HDAC inhibitors and Azacytidine. Epigenetics 10, 431-445.
  • Vogel T. and Lassmann S. (2014) Epigenetics: development, dynamics and disease. Cell Tissue Res 356, 451-455.
  • Fichter C.D., Gudernatsch V., Przypadlo C.M., Follo M., Schmidt G., Werner M. and Lassmann S. (2014) ErbB targeting inhibitors repress cell migration of esophageal squamous cell carcinoma and adenocarcinoma cells by distinct signaling pathways. J Mol Med (Berl) 92, 1209-1223.
  • Ahrens T.D., Werner M. and Lassmann S. (2014) Epigenetics in esophageal cancers. Cell Tissue Res 356, 643-655.